Molecules

Editorial

1 pages, 132 KiB

Open AccessEditorial

Dr. Kenneth A. Jacobson: First Winner of the Tu Youyou Award, in Honor of the Co-Recipient of the 2015 Nobel Prize in Physiology or Medicine

by Derek J. McPhee

Molecules 2016, 21(12), 1656; https://doi.org/10.3390/molecules21121656 - 1 Dec 2016

Cited by 2 | Viewed by 3718

Abstract

On behalf of MDPI, the journal Molecules, its Editorial Board and the award selection committee, whose diligent work evaluating the more than 50 outstanding quality nominations received for the award is gratefully acknowledged, it is with great pleasure that I announce that the [...] Read more.

On behalf of MDPI, the journal Molecules, its Editorial Board and the award selection committee, whose diligent work evaluating the more than 50 outstanding quality nominations received for the award is gratefully acknowledged, it is with great pleasure that I announce that the winner of the 2016 TU YOUYOU AWARD, sponsored by MDPI, is Dr. KENNETH A. JACOBSON, currently the Section Chief of the Molecular Recognition Section of the Laboratory of Bioorganic Chemistry (LBC) and Lab Chief of the LBC at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health in Bethesda, MD, USA.[...] Full article

2 pages, 143 KiB

Open AccessEditorial

Special Issue “Ring-Opening Polymerization”

by Takeshi Endo and Atsushi Sudo

Molecules 2016, 21(12), 1720; https://doi.org/10.3390/molecules21121720 - 14 Dec 2016

Viewed by 4247

Abstract

Ring-opening polymerization (ROP) has gained much attention because of its usefulness to synthesize polymers with main chains inheriting the heteroatoms and functional groups from the corresponding monomers.[...] Full article

(This article belongs to the Special Issue Ring-Opening Polymerization)

5 pages, 169 KiB

Open AccessEditorial

Special Issue: “Molecules against Alzheimer”

by Michael Decker and Diego Muñoz-Torrero

Molecules 2016, 21(12), 1736; https://doi.org/10.3390/molecules21121736 - 16 Dec 2016

Cited by 3 | Viewed by 6688

Abstract

This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder [...] Read more.

This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

3 pages, 145 KiB

Open AccessEditorial

Natural Products in Anti-Obesity Therapy

by Filomena Conforti and Min-Hsiung Pan

Molecules 2016, 21(12), 1750; https://doi.org/10.3390/molecules21121750 - 20 Dec 2016

Cited by 14 | Viewed by 5427

Abstract

Obesity is regulated by genetic, endocrine, metabolic, neurological, pharmacological, environmental, and nutritional factors. [...]
Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

2 pages, 151 KiB

Open AccessEditorial

Recent Advances in Olefin Metathesis

by Georgios C. Vougioukalakis

Molecules 2016, 21(12), 1751; https://doi.org/10.3390/molecules21121751 - 21 Dec 2016

Cited by 2 | Viewed by 4927

Abstract

Olefin metathesis is one of the most significant developments of the last 20 years in the fields of organic chemistry, polymers synthesis, and materials science [1–7]. [...]
Full article

(This article belongs to the Special Issue Olefin Metathesis)

Research

Jump to: Editorial, Review, Other

11 pages, 1605 KiB

Open AccessArticle

Combating Ebola with Repurposed Therapeutics Using the CANDO Platform

by Gaurav Chopra, Sashank Kaushik, Peter L. Elkin and Ram Samudrala

Molecules 2016, 21(12), 1537; https://doi.org/10.3390/molecules21121537 - 25 Nov 2016

Cited by 38 | Viewed by 7242

Abstract

Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to [...] Read more.

Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks. We have developed a Computational Analysis of Novel Drug Opportunities (CANDO) platform based on the hypothesis that drugs function by interacting with multiple protein targets to create a molecular interaction signature that can be exploited for rapid therapeutic repurposing and discovery. We used the CANDO platform to identify and rank FDA-approved drug candidates that bind and inhibit all proteins encoded by the genomes of five different Ebola virus strains. Top ranking drug candidates for EVD treatment generated by CANDO were compared to in vitro screening studies against Ebola virus-like particles (VLPs) by Kouznetsova et al. and genetically engineered Ebola virus and cell viability studies by Johansen et al. to identify drug overlaps between the in virtuale and in vitro studies as putative treatments for future EVD outbreaks. Our results indicate that integrating computational docking predictions on a proteomic scale with results from in vitro screening studies may be used to select and prioritize compounds for further in vivo and clinical testing. This approach will significantly reduce the lead time, risk, cost, and resources required to determine efficacious therapies against future EVD outbreaks. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

► Show Figures

Figure 1

17 pages, 3234 KiB

Open AccessArticle

Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity

by Hui Wang, Xin Cheng, Shujun Kong, Zixian Yang, Hongmei Wang, Qiuyan Huang, Jingyu Li, Cheng Chen and Yunshu Ma

Molecules 2016, 21(12), 1555; https://doi.org/10.3390/molecules21121555 - 28 Nov 2016

Cited by 20 | Viewed by 6470

Abstract

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, [...] Read more.

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl₃, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl₂. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayed antiarrhythmic effects in the CHCl₃-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl₃ (p < 0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl₂ (p < 0.01), and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD₅₀ = 59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton. Full article

► Show Figures

Graphical abstract

13 pages, 1866 KiB

Open AccessArticle

Effects of Polysaccharide Elicitors from Endophytic Fusarium oxysporum Fat9 on the Growth, Flavonoid Accumulation and Antioxidant Property of Fagopyrum tataricum Sprout Cultures

by Lingyun Zhong, Bei Niu, Lin Tang, Fang Chen, Gang Zhao and Jianglin Zhao

Molecules 2016, 21(12), 1590; https://doi.org/10.3390/molecules21121590 - 25 Nov 2016

Cited by 34 | Viewed by 5739

Abstract

The purpose of this study was to evaluate the effects of four different fungal polysaccharides, named water-extracted mycelia polysaccharide (WPS), sodium hydroxide-extracted mycelia polysaccharide (SPS), hydrochloric-extracted mycelia polysaccharide (APS), and exo-polysaccharide (EPS) obtained from the endophytic Fusarium oxysporum Fat9 on the sprout growth, [...] Read more.

The purpose of this study was to evaluate the effects of four different fungal polysaccharides, named water-extracted mycelia polysaccharide (WPS), sodium hydroxide-extracted mycelia polysaccharide (SPS), hydrochloric-extracted mycelia polysaccharide (APS), and exo-polysaccharide (EPS) obtained from the endophytic Fusarium oxysporum Fat9 on the sprout growth, flavonoid accumulation, and antioxidant capacity of tartary buckwheat. Without visible changes in the appearance of the sprouts, the exogenous polysaccharide elicitors strongly stimulated sprout growth and flavonoid production, and the stimulation effect was closely related with the polysaccharide (PS) species and its treatment dosage. With application of 200 mg/L of EPS, 200 mg/L of APS, 150 mg/L of WPS, or 100 mg/L of SPS, the total rutin and quercetin yields of buckwheat sprouts were significantly increased to 41.70 mg/(100 sprouts), 41.52 mg/(100 sprouts), 35.88 mg/(100 sprouts), and 32.95 mg/(100 sprouts), respectively. This was about 1.11 to 1.40-fold compared to the control culture of 31.40 mg/(100 sprouts). Moreover, the antioxidant capacity of tartary buckwheat sprouts was also enhanced after treatment with the four PS elicitors. Furthermore, the present study revealed the polysaccharide elicitation that caused the accumulation of functional flavonoid by stimulating the phenylpropanoid pathway. The application of beneficial fungal polysaccharide elicitors may be an effective approach to improve the nutritional and functional characteristics of tartary buckwheat sprouts. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

12 pages, 2006 KiB

Open AccessArticle

Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport

by Zheng-Gen Liao, Tao Tang, Xue-Jing Guan, Wei Dong, Jing Zhang, Guo-Wei Zhao, Ming Yang and Xin-Li Liang

Molecules 2016, 21(12), 1606; https://doi.org/10.3390/molecules21121606 - 24 Nov 2016

Cited by 23 | Viewed by 6102

Abstract

P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the [...] Read more.

P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors. Full article

(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)

► Show Figures

Figure 1

14 pages, 2201 KiB

Open AccessArticle

Extraction of Opuntia dillenii Haw. Polysaccharides and Their Antioxidant Activities

by Heng Li, Qingxia Yuan, Xianjiao Zhou, Fuhua Zeng and Xiangyang Lu

Molecules 2016, 21(12), 1612; https://doi.org/10.3390/molecules21121612 - 24 Nov 2016

Cited by 18 | Viewed by 6789

Abstract

Use of natural polysaccharides in medicine and food has wide interest in research. In this study, we extracted and purified some polysaccharides from cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products were characterized. Under the optimal purification conditions, the yield [...] Read more.

Use of natural polysaccharides in medicine and food has wide interest in research. In this study, we extracted and purified some polysaccharides from cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products were characterized. Under the optimal purification conditions, the yield of ODP extracted from the 2–4 month-old Opuntia dillenii Haw. (T-ODP) was 30.60% ± 0.40%, higher than that of ODP from the 5–10 month-old materials (O-ODP) (18.97% ± 0.58%). The extracted ODP was purified by DEAE sepharose fast flow anion exchange and Sephacryl S-400 chromatography with four fractions obtained (ODP-Ia, ODP-Ib, ODP-IIa and ODP-IIb). Analysis with UV-vis chromatography indicated that ODP-Ia and ODP-IIa were relatively homogeneous molecules with a molecular weight of 339 kD and 943 kD, respectively. Results of infrared spectroscopy indicated that ODP, ODP-Ia, and ODP-IIa were acidic polysaccharides. Further, the antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical, hydroxyl radicals, and superoxide radical in vitro demonstrated that the T-ODP exhibited higher antioxidant activity than the O-ODP, and the purified fraction (ODP-Ia) was superior to the ODP. These results will offer a theoretical basis for further research on the structure-function relationship of ODP and the rational utilization of Opuntia dillenii Haw. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

► Show Figures

Graphical abstract

19 pages, 2684 KiB

Open AccessArticle

Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms

by Bekzod Khakimov, Li Hong Tseng, Markus Godejohann, Søren Bak and Søren Balling Engelsen

Molecules 2016, 21(12), 1614; https://doi.org/10.3390/molecules21121614 - 24 Nov 2016

Cited by 31 | Viewed by 11251

Abstract

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene [...] Read more.

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

► Show Figures

Graphical abstract

8 pages, 1605 KiB

Open AccessArticle

A Novel Lighting OLED Panel Design

by Enyang Zhang, Weigao Xia and Xiaojian Yan

Molecules 2016, 21(12), 1615; https://doi.org/10.3390/molecules21121615 - 25 Nov 2016

Cited by 7 | Viewed by 7362

Abstract

A novel OLED (organic light emitting diode) lighting panel, which uses a special layout design, can reduce the photolithography cycles and process costs and is more reliable. It only needs two steps of photolithography cycles, which include an ITO (InSnO compound transparent oxide) [...] Read more.

A novel OLED (organic light emitting diode) lighting panel, which uses a special layout design, can reduce the photolithography cycles and process costs and is more reliable. It only needs two steps of photolithography cycles, which include an ITO (InSnO compound transparent oxide) pattern and insulator pattern. There is no need for the metal bus pattern of the ordinary design. The OLED device structure is a type of red–green–blue (RGB)-stacked emitting layer that has a good color index and greater adjustability, which improves the performance of the device. This novel design has the same equipment and material requirement compared to the ordinary design, and it is very beneficial in terms of high volume and low-cost production. It uses a hyper driving method because the entire OLED lighting panel is divided into many sub-emitting units; if one of the sub-emitting units is burned out, it has no effect on the adjacent sub-emitting unit, so the reliability is markedly better than the ordinary design. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

► Show Figures

Figure 1

9 pages, 1847 KiB

Open AccessArticle

Evaluation and Comparison of the Inhibition Effect of Astragaloside IV and Aglycone Cycloastragenol on Various UDP-Glucuronosyltransferase (UGT) Isoforms

by Ruixue Ran, Chunze Zhang, Rongshan Li, Bowei Chen, Weihua Zhang, Zhenying Zhao, Zhiwei Fu, Zuo Du, Xiaolang Du, Xiaolong Yang and Zhongze Fang

Molecules 2016, 21(12), 1616; https://doi.org/10.3390/molecules21121616 - 29 Nov 2016

Cited by 37 | Viewed by 6366

Abstract

As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in [...] Read more.

As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in this article was carried out to investigate the inhibition effects of AST and CAG on UDP-glucuronosyltransferases (UGTs) to explore potential clinical toxicity. An in vitro UGTs incubation mixture was employed to study the inhibition of AST and CAG towards UGT isoforms. Concentrations of 100 μM for each compound were used to initially screen the inhibitory efficiency. Deglycosylation of AST to CAG could strongly increase the inhibitory effects towards almost all of the tested UGT isoforms, with an IC₅₀ of 0.84 μM and 11.28 μM for UGT1A8 and UGT2B7, respectively. Ulteriorly, the inhibition type and kinetics of CAG towards UGT1A8 and UGT2B7 were evaluated depending on the initial screening results. Data fitting using Dixon and Lineweaver–Burk plots demonstrated that CAG competitively inhibited UGT1A8 and noncompetitively inhibited UGT2B7. From the second plot drawn with the slopes from the Lineweaver–Burk plot versus the concentrations of CAG, the inhibition constant (Ki) was calculated to be 0.034 μM and 20.98 μM for the inhibition of UGT1A8 and UGT2B7, respectively. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1 > [I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), it was successfully predicted here that an in vivo herb–drug interaction between AST/CAG and drugs mainly undergoing UGT1A8- or UGT2B7-catalyzed metabolism might occur when the plasma concentration of CAG is above 0.034 μM and 20.98 μM, respectively. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Figure 1

12 pages, 2812 KiB

Open AccessArticle

Charge Transfer Enhancement in the D-π-A Type Porphyrin Dyes: A Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) Study

by Guo-Jun Kang, Chao Song and Xue-Feng Ren

Molecules 2016, 21(12), 1618; https://doi.org/10.3390/molecules21121618 - 25 Nov 2016

Cited by 11 | Viewed by 7907

Abstract

The electronic geometries and optical properties of two D-π-A type zinc porphyrin dyes (NCH₃-YD2 and TPhe-YD) were systematically investigated by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to reveal the origin of significantly altered charge transfer enhancement by [...] Read more.

The electronic geometries and optical properties of two D-π-A type zinc porphyrin dyes (NCH₃-YD2 and TPhe-YD) were systematically investigated by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to reveal the origin of significantly altered charge transfer enhancement by changing the electron donor of the famous porphyrin-based sensitizer YD2-o-C8. The molecular geometries and photophysical properties of dyes before and after binding to the TiO₂ cluster were fully investigated. From the analyses of natural bond orbital (NBO), extended charge decomposition analysis (ECDA), and electron density variations (Δρ) between the excited state and ground state, it was found that the introduction of N(CH₃)₂ and 1,1,2-triphenylethene groups enhanced the intramolecular charge-transfer (ICT) character compared to YD2-o-C8. The absorption wavelength and transition possess character were significantly influenced by N(CH₃)₂ and 1,1,2-triphenylethene groups. NCH₃-YD2 with N(CH₃)₂ groups in the donor part is an effective way to improve the interactions between the dyes and TiO₂ surface, light having efficiency (LHE), and free energy change (ΔG_inject), which is expected to be an efficient dye for use in dye-sensitized solar cells (DSSCs). Full article

(This article belongs to the Special Issue Dye‐Sensitized Solar Cells)

► Show Figures

Figure 1

10 pages, 3778 KiB

Open AccessArticle

A New Two-Photon Ratiometric Fluorescent Probe for Detecting Alkaline Phosphatase in Living Cells

by Xiaohong Zhou, Yuren Jiang, Xiongjie Zhao and Yao Zhu

Molecules 2016, 21(12), 1619; https://doi.org/10.3390/molecules21121619 - 25 Nov 2016

Cited by 21 | Viewed by 7822

Abstract

Alkaline phosphatase (ALP) is an important diagnostic indicator of many human diseases. To quantitatively track ALP in biosystems, herein, for the first time, we report an efficient two-photon ratiometric fluorescent probe, termed probe 1 and based on classic naphthalene derivatives with a donor–π–acceptor [...] Read more.

Alkaline phosphatase (ALP) is an important diagnostic indicator of many human diseases. To quantitatively track ALP in biosystems, herein, for the first time, we report an efficient two-photon ratiometric fluorescent probe, termed probe 1 and based on classic naphthalene derivatives with a donor–π–acceptor (D–π–A) structure and deprotection of the phosphoric acid moiety by ALP. The presence of ALP causes the cleave of the phosphate group from naphthalene derivatives and the phosphate group changes the ability of the intramolecular charge transfer (ICT) and remarkably alters the probe’s photophysical properties, thus an obvious ratiometric signal with an isoemissive point is observed. The fluorescence intensity ratio displayed a linear relationship against the concentration of ALP in the concentration range from 20 to 180 U/L with the limit of detection of 2.3 U/L. Additionally, the probe 1 is further used for fluorescence imaging of ALP in living cells under one-photon excitation (405 nm) or two-photon excitation (720 nm), which showed a high resolution imaging, thus demonstrating its practical application in biological systems. Full article

► Show Figures

Figure 1

16 pages, 4453 KiB

Open AccessArticle

Hydrodechlorination of Tetrachloromethane over Palladium Catalysts Supported on Mixed MgF₂-MgO Carriers

by Magdalena Bonarowska, Maria Wojciechowska, Maciej Zieliński, Angelika Kiderys, Michał Zieliński, Piotr Winiarek and Zbigniew Karpiński

Molecules 2016, 21(12), 1620; https://doi.org/10.3390/molecules21121620 - 25 Nov 2016

Cited by 8 | Viewed by 6612

Abstract

Pd/MgO, Pd/MgF₂ and Pd/MgO-MgF₂ catalysts were investigated in the reaction of CCl₄ hydrodechlorination. All the catalysts deactivated in time on stream, but the degree of deactivation varied from catalyst to catalyst. The MgF₂-supported palladium with relatively large metal [...] Read more.

Pd/MgO, Pd/MgF₂ and Pd/MgO-MgF₂ catalysts were investigated in the reaction of CCl₄ hydrodechlorination. All the catalysts deactivated in time on stream, but the degree of deactivation varied from catalyst to catalyst. The MgF₂-supported palladium with relatively large metal particles appeared the best catalyst, characterized by good activity and selectivity to C₂-C₅ hydrocarbons. Investigation of post-reaction catalyst samples allowed to find several details associated with the working state of hydrodechlorination catalysts. The role of support acidity was quite complex. On the one hand, a definite, although not very high Lewis acidity of MgF₂ is beneficial for shaping high activity of palladium catalysts. The MgO-MgF₂ support characterized by stronger Lewis acidity than MgF₂ contributes to very good catalytic activity for a relatively long reaction period (~5 h) but subsequent neutralization of stronger acid centers (by coking) eliminates them from the catalyst. On the other hand, the role of acidity evolution, which takes place when basic supports (like MgO) are chlorided during HdCl reactions, is difficult to assess because different events associated with distribution of chlorided support species, leading to partial or even full blocking of the surface of palladium, which plays the role of active component in HdCl reactions. Full article

(This article belongs to the Special Issue Nano-sized Metal Fluorides: Novel Approaches to Lewis Acid Catalysts)

► Show Figures

Figure 1

16 pages, 2030 KiB

Open AccessArticle

Immobilization of Neutral Protease from Bacillus subtilis for Regioselective Hydrolysis of Acetylated Nucleosides: Application to Capecitabine Synthesis

by Teodora Bavaro, Giulia Cattaneo, Immacolata Serra, Ilaria Benucci, Massimo Pregnolato and Marco Terreni

Molecules 2016, 21(12), 1621; https://doi.org/10.3390/molecules21121621 - 25 Nov 2016

Cited by 25 | Viewed by 7652

Abstract

This paper describes the immobilization of the neutral protease from Bacillus subtilis and its application in the regioselective hydrolysis of acetylated nucleosides, including building blocks useful for the preparation of anticancer products. Regarding the immobilization study, different results have been obtained depending on [...] Read more.

This paper describes the immobilization of the neutral protease from Bacillus subtilis and its application in the regioselective hydrolysis of acetylated nucleosides, including building blocks useful for the preparation of anticancer products. Regarding the immobilization study, different results have been obtained depending on the immobilization procedure. Epoxy hydrophobic carriers gave a poorly stable derivative that released almost 50% of the immobilized protein under the required reaction conditions. On the contrary, covalent immobilization on a differently activated hydrophilic carrier (agarose) resulted in very stable enzyme derivatives. In an attempt to explain the obtained enzyme immobilization results, the hypothetical localization of lysines on the enzyme surface was predicted in a 3D structure model of B. subtilis protease N built in silico by using the structure of Staphylococcus aureus metalloproteinase as the template. The immobilized enzyme shown a high regioselectivity in the hydrolysis of different peracetylated nucleosides. A stable enzyme derivative was obtained and successfully used in the development of efficient preparative bioprocesses for the hydrolysis of acetylated nucleosides, giving new intermediates for the synthesis of capecitabine in high yield. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

► Show Figures

Figure 1

18 pages, 1392 KiB

Open AccessArticle

In Vitro Chemopreventive Properties of Green Tea, Rooibos and Honeybush Extracts in Skin Cells

by Tandeka U. Magcwebeba, Pieter Swart, Sonja Swanevelder, Elizabeth Joubert and Wentzel C. A. Gelderblom

Molecules 2016, 21(12), 1622; https://doi.org/10.3390/molecules21121622 - 25 Nov 2016

Cited by 25 | Viewed by 7586

Abstract

The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative [...] Read more.

The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative and pro-apoptotic activity of methanol and aqueous extracts of rooibos and two Cyclopia species in different skin cells, using green tea (Camellia sinensis) as a benchmark. Extracts were also characterised for their major individual polyphenols by high performance liquid chromatography and spectroscopically for the total polyphenol (TP) groups. The methanol extract of rooibos, containing higher levels of polyphenols than its aqueous extract, displayed similar activity to green tea as it selectively targeted premalignant cells by inhibiting cell proliferation at lower concentrations whilst inducing apoptosis via membrane depolarisation at higher concentrations. Specific roles of the major rooibos dihydrochalcones and flavanol/proanthocyanidin-type (FLAVA) compounds are likely to be involved. The aqueous extracts of the Cyclopia species were more active against cell proliferation and at inducing apoptosis which was associated with a higher FLAVA content and a reduced TP/FLAVA ratio. In contrast, their methanol extracts exhibited a cytoprotective effect against apoptosis which was related to their monomeric xanthone and flavanone content. The underlying chemopreventive properties of green tea and the herbal teas appear to be associated with diverse and complex monomeric/polymeric polyphenolic cell interactions. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

► Show Figures

Figure 1

12 pages, 1534 KiB

Open AccessArticle

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti

by Haonan Zhou, Pengjie Zhang, Zhiguo Hou, Jiabin Xie, Yuming Wang, Bin Yang, Yanyan Xu and Yubo Li

Molecules 2016, 21(12), 1623; https://doi.org/10.3390/molecules21121623 - 25 Nov 2016

Cited by 21 | Viewed by 6932

Abstract

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, [...] Read more.

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Graphical abstract

8 pages, 641 KiB

Open AccessCommunication

Effect of Thermoultrasound on the Antioxidant Compounds and Fatty Acid Profile of Blackberry (Rubus fruticosus spp.) Juice

by José De Jesús Manríquez-Torres, José Antonio Sánchez-Franco, Esther Ramírez-Moreno, Nelly Del Socorro Cruz-Cansino, José Alberto Ariza-Ortega and Jesús Martín Torres-Valencia

Molecules 2016, 21(12), 1624; https://doi.org/10.3390/molecules21121624 - 29 Nov 2016

Cited by 8 | Viewed by 6242

Abstract

Blackberry (Rubus fruticosus spp.) fruit has high antioxidant activity due to its significant content of anthocyanins and antioxidant compounds. Among emerging technologies for food preservation, thermoultrasound is a technique that reduces microbial loads and releases compounds with antioxidant properties. The objective of [...] Read more.

Blackberry (Rubus fruticosus spp.) fruit has high antioxidant activity due to its significant content of anthocyanins and antioxidant compounds. Among emerging technologies for food preservation, thermoultrasound is a technique that reduces microbial loads and releases compounds with antioxidant properties. The objective of this study was to determine the antioxidant content and fatty acid profile of blackberry juice subjected to thermoultrasound treatment in comparison to pasteurized juice. Blackberry juice and n-hexane extracts from a control (untreated juice), pasteurized, and thermoultrasonicated samples were evaluated for antioxidant activity, fatty acid profile, and antioxidant content. The juice treated with thermoultrasound exhibited significantly (p < 0.05) higher levels of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 µmol TE/L) in comparison to the control and pasteurized samples. Oil extract from thermoultrasound juice also had the highest antioxidant activity (177.5 mg VCEAC/L and 1802.6 µmol TE/L). The fatty acid profile of the n-hexane extracts showed the presence of myristic, linolenic, stearic, oleic, and linoleic acids and was not affected by the treatments except for stearic acid, whose amount was particularly higher in the control. Our results demonstrated that thermoultrasound can be an alternative technology to pasteurization that maintains and releases antioxidant compounds and preserves the fatty acids of fruit juice. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

► Show Figures

Graphical abstract

8 pages, 1364 KiB

Open AccessArticle

A Method for Determining the Content of Glycoproteins in Biological Samples

by Yang Gao, Duoduo Xu, Hongyue Li, Xianling Yang, Mingxing Wang and Qipin Gao

Molecules 2016, 21(12), 1625; https://doi.org/10.3390/molecules21121625 - 26 Nov 2016

Cited by 3 | Viewed by 5772

Abstract

The glycoprotein purified from the mycelium extract of Tremella fuciformis was marked with iodine through the iodine substitution reaction. The content of iodine, which is indicative of the amount of the marked tremella glycoprotein (ITG), was detected with Inductively coupled plasma mass spectrometry [...] Read more.

The glycoprotein purified from the mycelium extract of Tremella fuciformis was marked with iodine through the iodine substitution reaction. The content of iodine, which is indicative of the amount of the marked tremella glycoprotein (ITG), was detected with Inductively coupled plasma mass spectrometry (ICP-MS). The method was found to be stable, sensitive, and accurate at detecting the content of iodine-substituted glycoprotein, and was used in the quantitative analysis of biological samples, including blood and organs. Different biological samples were collected from rats after oral administration of ITG, and were tested for iodine content by ICP-MS to calculate the amount of ITG in the samples. The results suggested that ICP-MS is a sensitive, stable, and accurate method for detection of iodinated glycoproteins in blood and organs. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

► Show Figures

Figure 1

15 pages, 3167 KiB

Open AccessArticle

Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans

by Ángel Gabriel Díaz-Sánchez, Emilio Alvarez-Parrilla, Alejandro Martínez-Martínez, Luis Aguirre-Reyes, Jesica Aline Orozpe-Olvera, Miguel Armando Ramos-Soto, José Alberto Núñez-Gastélum, Bonifacio Alvarado-Tenorio and Laura Alejandra De la Rosa

Molecules 2016, 21(12), 1628; https://doi.org/10.3390/molecules21121628 - 26 Nov 2016

Cited by 33 | Viewed by 10630

Abstract

Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, [...] Read more.

Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2′-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a “hinge” located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

► Show Figures

Graphical abstract

25 pages, 2812 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type

by Kristina Pavić, Ivana Perković, Petra Gilja, Filip Kozlina, Katja Ester, Marijeta Kralj, Dominique Schols, Dimitra Hadjipavlou-Litina, Eleni Pontiki and Branka Zorc

Molecules 2016, 21(12), 1629; https://doi.org/10.3390/molecules21121629 - 28 Nov 2016

Cited by 31 | Viewed by 9012

Abstract

In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a–k) are reported. In the first series of compounds, PQ [...] Read more.

In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a–k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a–k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e), benzodioxole (7f), p-Cl (7g) and m-CF₃ (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC₅₀ = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Scheme 1

13 pages, 1441 KiB

Open AccessArticle

Simultaneous Determination of Four Tanshinones by UPLC-TQ/MS and Their Pharmacokinetic Application after Administration of Single Ethanol Extract of Danshen Combined with Water Extract in Normal and Adenine-Induced Chronic Renal Failure Rats

by Hong-Die Cai, Shu-Lan Su, Yonghui Li, Zhenhua Zhu, Jianming Guo, Yue Zhu, Sheng Guo, Dawei Qian and Jinao Duan

Molecules 2016, 21(12), 1630; https://doi.org/10.3390/molecules21121630 - 28 Nov 2016

Cited by 22 | Viewed by 5711

Abstract

Salvia miltiorrhiza, one of the major traditional Chinese medicines, is commonly used and the main active ingredients—tanshinones—possess the ability to improve renal function. In this paper, the UPLC-TQ/MS method of simultaneously determining four tanshinones—tanshinone IIA, dihydrotanshinone I, tanshinone I, and cryptotanshinone—was established [...] Read more.

Salvia miltiorrhiza, one of the major traditional Chinese medicines, is commonly used and the main active ingredients—tanshinones—possess the ability to improve renal function. In this paper, the UPLC-TQ/MS method of simultaneously determining four tanshinones—tanshinone IIA, dihydrotanshinone I, tanshinone I, and cryptotanshinone—was established and applied to assess the pharmacokinetics in normal and chronic renal failure (CRF) rat plasma. The pharmacokinetics of tanshinones in rats were studied after separately intragastric administration of Salvia miltiorrhiza ethanol extract (SMEE) (0.65 g/kg), SMEE (0.65 g/kg) combined with Salvia miltiorrhiza water extract (SMWE) (1.55 g/kg). The results showed C_max and AUC_0–t of tanshinone IIA, tanshinone I, cryptotanshinone reduced by 50%~80% and CLz/F increased by 2~4 times (p < 0.05) in model group after administrated with SMEE. Nevertheless, after intragastric administration of a combination of SMWE and SMEE, the C_max and AUC_0–t of four tanshinones were upregulated and CLz/F was downregulated, which undulated similarity from the model group to the normal group with compatibility of SMEE and SMWE. These results hinted that SMWE could improve the bioavailability of tanshinones in CRF rats, which provides scientific information for further exploration the mechanism of the combination of SMWE and SMEE and offers a reference for clinical administration of Salvia miltiorrhiza. Full article

► Show Figures

Graphical abstract

9 pages, 965 KiB

Open AccessArticle

Antifungal Activity of Oleuropein against Candida albicans—The In Vitro Study

by Nataša Zorić, Nevenka Kopjar, Ivan Bobnjarić, Igor Horvat, Siniša Tomić and Ivan Kosalec

Molecules 2016, 21(12), 1631; https://doi.org/10.3390/molecules21121631 - 28 Nov 2016

Cited by 25 | Viewed by 9164

Abstract

In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value [...] Read more.

In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL⁻¹. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

► Show Figures

Figure 1

15 pages, 2490 KiB

Open AccessArticle

Expression, Purification, and Characterization of Interleukin-11 Orthologues

by Andrei S. Sokolov, Alexei S. Kazakov, Valery V. Solovyev, Ramis G. Ismailov, Vladimir N. Uversky, Yulia S. Lapteva, Roman V. Mikhailov, Ekaterina V. Pavlova, Iana O. Terletskaya, Ludmila V. Ermolina, Sergei E. Permyakov and Eugene A. Permyakov

Molecules 2016, 21(12), 1632; https://doi.org/10.3390/molecules21121632 - 29 Nov 2016

Cited by 6 | Viewed by 7669

Abstract

Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we [...] Read more.

Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11. Hence, the evolutionary divergence does not impair IL-11 signaling. Furthermore, compared to human rIL-11 its macaque orthologue is 8-fold more effective STAT3 activator, which favors its use for treatment of thrombocytopenia as a potent substitute for human rIL-11. Compared to IL-6, IL-11 signaling exhibits lower species specificity, likely due to less conserved intrinsic disorder propensity within IL-6 orthologues. The developed express method for preparation of functionally active macaque/mouse rIL-11 samples is suited for exploration of the molecular mechanisms underlying IL-11 action and for development of the drug candidates for therapy of oncologic/hematologic/inflammatory diseases related to IL-11 signaling. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

22 pages, 3660 KiB

Open AccessArticle

Enhanced Antimicrobial and Anticancer Activity of Silver and Gold Nanoparticles Synthesised Using Sargassum incisifolium Aqueous Extracts

by Mokone Mmola, Marilize Le Roes-Hill, Kim Durrell, John J. Bolton, Nicole Sibuyi, Mervin E. Meyer, Denzil R. Beukes and Edith Antunes

Molecules 2016, 21(12), 1633; https://doi.org/10.3390/molecules21121633 - 2 Dec 2016

Cited by 68 | Viewed by 9001

Abstract

A detailed, methodical approach was used to synthesise silver and gold nanoparticles using two differently prepared aqueous extracts of the brown algae Sargassum incisifolium. The efficiency of the extracts in producing nanoparticles were compared to commercially available brown algal fucoidans, a major [...] Read more.

A detailed, methodical approach was used to synthesise silver and gold nanoparticles using two differently prepared aqueous extracts of the brown algae Sargassum incisifolium. The efficiency of the extracts in producing nanoparticles were compared to commercially available brown algal fucoidans, a major constituent of brown algal aqueous extracts. The nanoparticles were characterised using TEM, XRD and UV/Vis spectroscopy and zeta potential measurements. The rate of nanoparticle formation was assessed using UV/Vis spectroscopy and related to the size, shape and morphology of the nanoparticles as revealed by TEM. The antioxidant, reducing power and total polyphenolic contents of the aqueous extracts and fucoidans were determined, revealing that the aqueous extracts with the highest contents produced smaller, spherical, more monodisperse nanoparticles at a faster rate. The nanoparticles were assessed against two gram-negative bacteria, two gram-positive bacteria and one yeast strain. In contrast to the literature, the silver nanoparticles produced using the aqueous extracts were particularly toxic to Gram-negative bacteria, while the gold nanoparticles lacked activity. The cytotoxic activity of the nanoparticles was also evaluated against cancerous (HT-29, MCF-7) and non-cancerous (MCF-12a) cell lines. The silver nanoparticles displayed selectivity, since the MCF-12a cell line was found to be resistant to the nanoparticles, while the cancerous HT-29 cell line was found to be sensitive (10% viability). The gold nanoparticles displayed negligible toxicity. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Applications)

► Show Figures

Graphical abstract

16 pages, 1959 KiB

Open AccessArticle

Synthesis and Pharmacological Evaluation of New 3,4-Dihydroisoquinolin Derivatives Containing Heterocycle as Potential Anticonvulsant Agents

by Hong-Jian Zhang, Qing-Kun Shen, Chun-Mei Jin and Zhe-Shan Quan

Molecules 2016, 21(12), 1635; https://doi.org/10.3390/molecules21121635 - 29 Nov 2016

Cited by 14 | Viewed by 5536

Abstract

Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4a–t and 9a–e) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, ¹H-NMR, [...] Read more.

Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4a–t and 9a–e) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and mass spectral data. Among them, 9-(exyloxy)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one (9a) showed significant anticonvulsant activity in MES tests with an ED₅₀ value of 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9). It showed much higher anticonvulsant activity than that of valproate. It also demonstrated potent activity against PTZ-induced seizures. A docking study of compound 9a in the benzodiazepine (BZD)-binding site of γ-aminobutyric acid_A (GABA_A) receptor confirmed possible binding of compound 9a with the BZD receptors. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

8 pages, 4948 KiB

Open AccessCommunication

Controlled Synthesis of Atomically Layered Hexagonal Boron Nitride via Chemical Vapor Deposition

by Juanjuan Liu, R. Govindan Kutty and Zheng Liu

Molecules 2016, 21(12), 1636; https://doi.org/10.3390/molecules21121636 - 29 Nov 2016

Cited by 20 | Viewed by 8024

Abstract

Hexagonal boron nitrite (h-BN) is an attractive material for many applications including electronics as a complement to graphene, anti-oxidation coatings, light emitters, etc. However, the synthesis of high-quality h-BN is still a great challenge. In this work, via controlled chemical vapor deposition, we [...] Read more.

Hexagonal boron nitrite (h-BN) is an attractive material for many applications including electronics as a complement to graphene, anti-oxidation coatings, light emitters, etc. However, the synthesis of high-quality h-BN is still a great challenge. In this work, via controlled chemical vapor deposition, we demonstrate the synthesis of h-BN films with a controlled thickness down to atomic layers. The quality of as-grown h-BN is confirmed by complementary characterizations including high-resolution transition electron microscopy, atomic force microscopy, Raman spectroscopy and X-ray photo-electron spectroscopy. This work will pave the way for production of large-scale and high-quality h-BN and its applications as well. Full article

(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)

► Show Figures

Figure 1

16 pages, 1950 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Aromatic Imide-Polyamine Conjugates

by Ming Li, Yuxia Wang, Jianying Zhang, Songqiang Xie, Chaojie Wang and Yingliang Wu

Molecules 2016, 21(12), 1637; https://doi.org/10.3390/molecules21121637 - 30 Nov 2016

Cited by 7 | Viewed by 5833

Abstract

Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting [...] Read more.

Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting tumor cell proliferation and inducing tumor cell apoptosis via ROS-mediated mitochondrial pathway. The in vivo assays on three H22 tumor transplant models revealed that compound 11e exerted potent ability in preventing lung cancer metastasis and extending lifespan. Furthermore, the efficacy of 11e in inhibiting tumor growth and improving body weight index were better than that of positive control, amonafide. Our study demonstrates that compound 11e is a valuable lead compound for further investigation. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

13 pages, 4517 KiB

Open AccessArticle

Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking

by Meimei Chen, Fafu Yang, Jie Kang, Xuemei Yang, Xinmei Lai and Yuxing Gao

Molecules 2016, 21(12), 1639; https://doi.org/10.3390/molecules21121639 - 29 Nov 2016

Cited by 9 | Viewed by 5193

Abstract

In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, [...] Read more.

In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

► Show Figures

Graphical abstract

13 pages, 4681 KiB

Open AccessArticle

Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy

by Chia-Chieh Wu, Yi-Fu Huang, Chen-Pu Hsieh, Pin-Ju Chueh and Yao-Li Chen

Molecules 2016, 21(12), 1640; https://doi.org/10.3390/molecules21121640 - 30 Nov 2016

Cited by 27 | Viewed by 6072

Abstract

Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of [...] Read more.

Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of human osteosarcoma MG-63 cells through enhanced oxidative stress and apoptosis. Interestingly, an inhibitor of osteoclast-mediated bone resorption, zoledronic acid (ZOL), also a third-generation nitrogen-containing bisphosphonate, is effective in the treatment of bone metastases in patients with various solid tumors. In this present study, we found that UA combined with ZOL to significantly suppress cell viability, colony formation, and induce apoptosis in two lines of human osteosarcoma cells. The pre-treatment of the antioxidant had reversed the oxidative stress and cell viability inhibition in the combined treatment, indicating that oxidative stress is important in the combined anti-tumor effects. Moreover, we demonstrated that ZOL combined with UA significantly induced autophagy and co-administration of autophagy inhibitor reduces the growth inhibitory effect of combined treatment. Collectively, these data shed light on the pathways involved in the combined effects of ZOL and UA that might serve as a potential therapy against osteosarcoma. Full article

► Show Figures

Graphical abstract

16 pages, 6244 KiB

Open AccessArticle

Docetaxel-Loaded Self-Assembly Stearic Acid-Modified Bletilla striata Polysaccharide Micelles and Their Anticancer Effect: Preparation, Characterization, Cellular Uptake and In Vitro Evaluation

by Qingxiang Guan, Dandan Sun, Guangyuan Zhang, Cheng Sun, Miao Wang, Danyang Ji and Wei Yang

Molecules 2016, 21(12), 1641; https://doi.org/10.3390/molecules21121641 - 2 Dec 2016

Cited by 41 | Viewed by 7006

Abstract

Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC) [...] Read more.

Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC) were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC). The hemolysis and in vitro anticancer activity were studied. Cellular uptake and apoptotic rate were measured using flow cytometry assay. Particle size, zeta potential, EE and LC were 125.30 ± 1.89 nm, −26.92 ± 0.18 mV, 86.6% ± 0.17%, and 14.8% ± 0.13%, respectively. The anticancer activities of DTX-SA-BSPs copolymer micelles against HepG2, HeLa, SW480, and MCF-7 (83.7% ± 1.0%, 54.5% ± 4.2%, 48.5% ± 4.2%, and 59.8% ± 1.4%, respectively) were superior to that of docetaxel injection (39.2% ± 1.1%, 44.5% ± 5.3%, 38.5% ± 5.4%, and 49.8% ± 2.9%, respectively) at 0.5 μg/mL drug concentration. The DTX release percentage of DTX-SA-BSPs copolymer micelles and docetaxel injection were 66.93% ± 1.79% and 97.06% ± 1.56% in two days, respectively. Cellular uptake of DTX-FITC-SA-BSPs copolymer micelles in cells had a time-dependent relation. Apoptotic rate of DTX-SA-BSPs copolymer micelles and docetaxel injection were 73.48% and 69.64%, respectively. The SA-BSPs copolymer showed good hemocompatibility. Therefore, SA-BSPs copolymer can be used as a carrier for delivering hydrophobic drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

7 pages, 2602 KiB

Open AccessArticle

Investigation on Fluorescence Quenching Mechanism of Perylene Diimide Dyes by Graphene Oxide

by Yuzhen Zhao, Kexuan Li, Zemin He, Yongming Zhang, Yang Zhao, Haiquan Zhang and Zongcheng Miao

Molecules 2016, 21(12), 1642; https://doi.org/10.3390/molecules21121642 - 30 Nov 2016

Cited by 17 | Viewed by 6211

Abstract

Perylene diimide derivatives were used as probes to investigate the effect of the molecular structures on the fluorescence quenching mechanism in a perylene diimide/graphene oxide system. The electrons transferred from the excited state of dyes to the conductive band of graphene oxide with [...] Read more.

Perylene diimide derivatives were used as probes to investigate the effect of the molecular structures on the fluorescence quenching mechanism in a perylene diimide/graphene oxide system. The electrons transferred from the excited state of dyes to the conductive band of graphene oxide with different concentrations were determined by fluorescence spectra. The results indicated that the quenching efficiency of perylene diimides by graphene oxide was not only dependent on the difference between the lowest unoccupied molecular orbital level of dyes and the conduction band of the graphene oxide, but also mainly on the difference in the molecular structures. Full article

► Show Figures

Figure 1

15 pages, 2499 KiB

Open AccessArticle

Drug Release by Direct Jump from Poly(ethylene-glycol-b-ε-caprolactone) Nano-Vector to Cell Membrane

by Ugo Till, Laure Gibot, Anne-Françoise Mingotaud, Jérôme Ehrhart, Luc Wasungu, Christophe Mingotaud, Jean-Pierre Souchard, Alix Poinso, Marie-Pierre Rols, Frédéric Violleau and Patricia Vicendo

Molecules 2016, 21(12), 1643; https://doi.org/10.3390/molecules21121643 - 30 Nov 2016

Cited by 12 | Viewed by 5057

Abstract

Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a [...] Read more.

Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers. This study showed that the cellular uptake and the phototoxicity of loaded Pheo-a are ten times higher than those of the free drug and revealed a very low cellular penetration of the fluorescence-labeled micelles. Neither loaded nor free Pheo-a displayed the same cellular localization as the labeled micelles. These results imply that the drug entered the cells without its carrier and probably without a disruption, as suggested by their stability in cell culture medium. These data allowed us to propose that Pheo-a directly migrates from the micelle to the cell without disruption of the vector. This mechanism will be discussed. Full article

► Show Figures

Figure 1

14 pages, 4074 KiB

Open AccessArticle

Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation

by Cristina Di Donato, Margherita Lavorgna, Roberto Fattorusso, Carla Isernia, Marina Isidori, Gaetano Malgieri, Concetta Piscitelli, Chiara Russo, Luigi Russo and Rosa Iacovino

Molecules 2016, 21(12), 1644; https://doi.org/10.3390/molecules21121644 - 1 Dec 2016

Cited by 44 | Viewed by 8426

Abstract

Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in [...] Read more.

Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 (breast cancer cell line), Hep G2 (hepatocyte carcinoma cell line), Caco-2 (colon adenocarcinoma cell line), and A-549 (alveolar basal epithelial carcinoma cell line). The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC₅₀ values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

► Show Figures

Figure 1

11 pages, 2196 KiB

Open AccessCommunication

Excited-State Dynamics of Melamine and Its Lysine Derivative Investigated by Femtosecond Transient Absorption Spectroscopy

by Yuyuan Zhang, Ashley A. Beckstead, Yuesong Hu, Xijun Piao, Dennis Bong and Bern Kohler

Molecules 2016, 21(12), 1645; https://doi.org/10.3390/molecules21121645 - 30 Nov 2016

Cited by 20 | Viewed by 9624

Abstract

Melamine may have been an important prebiotic information carrier, but its excited-state dynamics, which determine its stability under UV radiation, have never been characterized. The ability of melamine to withstand the strong UV radiation present on the surface of the early Earth is [...] Read more.

Melamine may have been an important prebiotic information carrier, but its excited-state dynamics, which determine its stability under UV radiation, have never been characterized. The ability of melamine to withstand the strong UV radiation present on the surface of the early Earth is likely to have affected its abundance in the primordial soup. Here, we studied the excited-state dynamics of melamine (a proto-nucleobase) and its lysine derivative (a proto-nucleoside) using the transient absorption technique with a UV pump, and UV and infrared probe pulses. For melamine, the excited-state population decays by internal conversion with a lifetime of 13 ps without coupling significantly to any photochemical channels. The excited-state lifetime of the lysine derivative is slightly longer (18 ps), but the dominant deactivation pathway is otherwise the same as for melamine. In both cases, the vast majority of excited molecules return to the electronic ground state on the aforementioned time scales, but a minor population is trapped in a long-lived triplet state. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

► Show Figures

Figure 1

10 pages, 936 KiB

Open AccessArticle

A Simple Precursor for Highly Functionalized Fused Imidazo[4,5-b]pyridines and Imidazo[4,5-b]-1,8-naphthyridine

by Omar K. Al-duaij, Magdi E.A. Zaki and Abdel-Rhman B. A. El Gazzar

Molecules 2016, 21(12), 1646; https://doi.org/10.3390/molecules21121646 - 1 Dec 2016

Cited by 8 | Viewed by 5180

Abstract

1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of [...] Read more.

1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of a base, or to 5,7-diamino-3-(4-alkyl aryl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile 8, and 6,8,9-triamino-3-(4-substitutedbenzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7-carbonitrile 10 in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU). Both reactions evolved from an adduct formed by nucleophilic attack of the malononitrile anion or 2-amino-1,1,3-propenetricarbonitrile anion to the carbon of the cyanoformimidoyl substituent. In the case of the malononitrile anion, a 5-amino-1-alkyl aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 7 was isolated when this reaction was carried out in the presence of DBU. The structure of compound 7 was confirmed by spectroscopic methods, and cyclized intramolecularly to 8 by heating in ethanol/triethyl amine. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Scheme 1

15 pages, 2270 KiB

Open AccessArticle

Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa)

by Yi-Xiao Li, Yong-Gui Pan, Feng-Ping He, Meng-Qi Yuan and Shang-Bin Li

Molecules 2016, 21(12), 1648; https://doi.org/10.3390/molecules21121648 - 1 Dec 2016

Cited by 27 | Viewed by 8236

Abstract

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to [...] Read more.

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC–MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

► Show Figures

Figure 1

13 pages, 377 KiB

Open AccessArticle

A Molecular Electron Density Theory Study of the Chemical Reactivity of Cis- and Trans-Resveratrol

by Juan Frau, Francisco Muñoz and Daniel Glossman-Mitnik

Molecules 2016, 21(12), 1650; https://doi.org/10.3390/molecules21121650 - 1 Dec 2016

Cited by 37 | Viewed by 6024

Abstract

The chemical reactivity of resveratrol isomers with the potential to play a role as inhibitors of the nonenzymatic glycation of amino acids and proteins, both acting as antioxidants and as chelating agents for metallic ions such as Cu, Al and Fe, have been [...] Read more.

The chemical reactivity of resveratrol isomers with the potential to play a role as inhibitors of the nonenzymatic glycation of amino acids and proteins, both acting as antioxidants and as chelating agents for metallic ions such as Cu, Al and Fe, have been studied by resorting to the latest family of Minnesota density functionals. The chemical reactivity descriptors have been calculated through Molecular Electron Density Theory encompassing Conceptual DFT. The active sites for nucleophilic and electrophilic attacks have been chosen by relating them to the Fukui function indices, the dual descriptor

f^{(2)} (r)

and the electrophilic and nucleophilic Parr functions. The validity of “Koopmans’ theorem in DFT” has been assessed by means of a comparison between the descriptors calculated through vertical energy values and those arising from the HOMO and LUMO values. Full article

(This article belongs to the Special Issue Density Functional Theory and Reactivity Indices: Applications in Organic Chemical Reactivity)

► Show Figures

Figure 1

11 pages, 5705 KiB

Open AccessArticle

Catalytic Performance of a New 1D Cu(II) Coordination Polymer {Cu(NO₃)(H₂O)}(HTae)(4,4′-Bpy) for Knoevenagel Condensation

by Edurne S. Larrea, Roberto Fernández de Luis and María I. Arriortua

Molecules 2016, 21(12), 1651; https://doi.org/10.3390/molecules21121651 - 1 Dec 2016

Cited by 4 | Viewed by 5316

Abstract

The {Cu(NO₃)(H₂O)}(HTae)(4,4′-Bpy) (H₂Tae = 1,1,2,2-tetraacetylethane, 4,4′-Bpy = 4,4′-Dipyridyl) 1D coordination polymer has been obtained by slow evaporation. The crystal structure consists of parallel and oblique {Cu(HTae)(4,4′-Bpy)} zig-zag metal–organic chains stacked along the [100] crystallographic direction. Copper(II) ions [...] Read more.

The {Cu(NO₃)(H₂O)}(HTae)(4,4′-Bpy) (H₂Tae = 1,1,2,2-tetraacetylethane, 4,4′-Bpy = 4,4′-Dipyridyl) 1D coordination polymer has been obtained by slow evaporation. The crystal structure consists of parallel and oblique {Cu(HTae)(4,4′-Bpy)} zig-zag metal–organic chains stacked along the [100] crystallographic direction. Copper(II) ions are in octahedral coordination environment linked to two nitrogen atoms of two bridging 4,4′-Bpy and to two oxygen atoms of one HTae molecule in the equatorial plane. The occupation of the axial positions varies from one copper atom to another, with different combinations of water molecules and nitrate anions, giving rise to a commensurate super-structure. By means of the thermal removal of water molecules, copper coordinatively unsaturated centres are obtained. These open metal sites could act as Lewis acid active sites in several heterogeneous catalytic reactions. The dehydrated compound, CuHTaeBpy_HT, has been tested as a heterogeneous recoverable catalyst for Knoevenagel condensation reactions. The catalyst is active and heterogeneous for the condensation of aldehydes with malononitrile at 60 °C using a molar ratio catalyst:substrate of 3 % and toluene as solvent. The catalyst suffers a partial loss of activity when reusing it, but can be reused at least four times. Full article

(This article belongs to the Special Issue Transition Metal Catalysis 2016)

► Show Figures

Graphical abstract

13 pages, 642 KiB

Open AccessArticle

Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS

by Zhou Tong, Yan-Can Wu, Qiong-Qiong Liu, Yan-Hong Shi, Li-Jun Zhou, Zhen-Yu Liu, Lin-Sheng Yu and Hai-Qun Cao

Molecules 2016, 21(12), 1652; https://doi.org/10.3390/molecules21121652 - 1 Dec 2016

Cited by 33 | Viewed by 5729

Abstract

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% [...] Read more.

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health. Full article

► Show Figures

Graphical abstract

13 pages, 967 KiB

Open AccessArticle

A Novel Two-Step Liquid-Liquid Extraction Procedure Combined with Stationary Phase Immobilized Human Serum Albumin for the Chiral Separation of Cetirizine Enantiomers along with M and P Parabens

by Aleksandra Chmielewska, Lucyna Konieczna and Tomasz Bączek

Molecules 2016, 21(12), 1654; https://doi.org/10.3390/molecules21121654 - 7 Dec 2016

Cited by 7 | Viewed by 7265

Abstract

The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage [...] Read more.

The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage forms, besides the active substance in large amounts there are usually also inactive ingredients such as methyl- and propylparaben. Unfortunately, these compounds can interfere with the analyte, inter alia during chiral separation of the analyte enantiomers. The proposed innovative two-step liquid-liquid extraction procedure allowed for the determination of cetirizine enantiomers (along with M and P parabens) also in liquid dosage forms. The main focus of this study was the chromatographic activity of cetirizine dihydrochloride on the proteinate-based chiral stationary phase. The chromatographic separation of cetirizine enantiomers was performed on an immobilized human serum albumin (HSA) column for the first time. Measurements were performed at a wavelength of 227 nm. Under optimal conditions, baseline separation of two enantiomers was obtained with 1.43 enantioseparation factor (α) and 1.82 resolution (R_s). Finally, the proposed method was successfully applied to the selected pharmaceutical formulations. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

► Show Figures

Graphical abstract

16 pages, 1699 KiB

Open AccessArticle

Expedient Organocatalytic Syntheses of 4-Substituted Pyrazolidines and Isoxazolidines

by Tarek Yousfi, Alysha Elliott, Messiad Hanane, Rachid Merdes and Albert Moyano

Molecules 2016, 21(12), 1655; https://doi.org/10.3390/molecules21121655 - 1 Dec 2016

Cited by 7 | Viewed by 6030

Abstract

The efficient organocatalytic synthesis of heterocyclic systems of biological relevance is a subject of growing interest. We have found that the pyrrolidine/benzoic acid-catalyzed reaction of α-substituted propenals such as methacrolein, 2-benzylpropenal and 2-(n-hexyl)propenal with activated hydrazines takes place in very good [...] Read more.

The efficient organocatalytic synthesis of heterocyclic systems of biological relevance is a subject of growing interest. We have found that the pyrrolidine/benzoic acid-catalyzed reaction of α-substituted propenals such as methacrolein, 2-benzylpropenal and 2-(n-hexyl)propenal with activated hydrazines takes place in very good yields (83%–99.6%) under very mild conditions to afford 4-substituted pyrazolidin-3-ols (as diastereomer mixtures); subsequent oxidation with PCC affords the corresponding-4-substituted-3-pyrazolidinones in essentially quantitative yields. In a similar way, 4-substituted isoxazolidinones are obtained with N-Cbz-hydroxylamine as a reagent. The use of chiral diarylprolinol trimethylsilyl ethers as catalysts allows the synthesis of several of these compounds in optically active form, in some cases with excellent enantioselectivity (up to 96:4 er). A preliminary evaluation of the biological activity shows that some of these compounds exhibit interesting antibacterial and antifungal activities. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

► Show Figures

Figure 1

10 pages, 3224 KiB

Open AccessArticle

A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions

by Maximiliano Martínez-Cifuentes, Boris Weiss-López and Ramiro Araya-Maturana

Molecules 2016, 21(12), 1658; https://doi.org/10.3390/molecules21121658 - 2 Dec 2016

Cited by 6 | Viewed by 6114

Abstract

In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents [...] Read more.

In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f⁺) and Parr (P⁺) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity. Full article

(This article belongs to the Special Issue Density Functional Theory and Reactivity Indices: Applications in Organic Chemical Reactivity)

► Show Figures

Graphical abstract

11 pages, 9874 KiB

Open AccessArticle

Supercritical CO₂ Foaming of Radiation Cross-Linked Isotactic Polypropylene in the Presence of TAIC

by Chen-Guang Yang, Mou-Hua Wang, Ming-Xing Zhang, Xiao-Hu Li, Hong-Long Wang, Zhe Xing, Lin-Feng Ye and Guo-Zhong Wu

Molecules 2016, 21(12), 1660; https://doi.org/10.3390/molecules21121660 - 7 Dec 2016

Cited by 53 | Viewed by 8115

Abstract

Since the maximum foaming temperature window is only about 4 °C for supercritical CO₂ (scCO₂) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO₂ [...] Read more.

Since the maximum foaming temperature window is only about 4 °C for supercritical CO₂ (scCO₂) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO₂ foaming. In this work, radiation cross-linked isotactic polypropylene, assisted by the addition of a polyfunctional monomer (triallylisocyanurate, TAIC), was employed in the scCO₂ foaming process in order to understand the benefits of radiation cross-linking. Due to significantly enhanced melt strength and the decreased degree of crystallinity caused by cross-linking, the scCO₂ foaming behavior of polypropylene was dramatically changed. The cell size distribution, cell diameter, cell density, volume expansion ratio, and foaming rate of radiation-cross-linked polypropylene under different foaming conditions were analyzed and compared. It was found that radiation cross-linking favors the foamability and formation of well-defined cell structures. The optimal absorbed dose with the addition of 2 wt % TAIC was 30 kGy. Additionally, the foaming temperature window was expanded to about 8 °C, making the handling of scCO₂ foaming of isotactic polypropylene much easier. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

► Show Figures

Graphical abstract

16 pages, 6944 KiB

Open AccessArticle

Janus Compounds, 5-Chloro-N⁴-methyl-N⁴-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, Cause Both Microtubule Depolymerizing and Stabilizing Effects

by Cristina C. Rohena, April L. Risinger, Ravi Kumar Vyas Devambatla, Nicholas F. Dybdal-Hargreaves, Roma Kaul, Shruti Choudhary, Aleem Gangjee and Susan L. Mooberry

Molecules 2016, 21(12), 1661; https://doi.org/10.3390/molecules21121661 - 2 Dec 2016

Cited by 7 | Viewed by 6615

Abstract

While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule [...] Read more.

While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule depolymerization and, surprisingly, with higher concentrations, microtubule bundles were also observed. There were subtle differences in the propensity to cause these competing effects among the compounds with a continuum of stabilizing and destabilizing effects. Tubulin polymerization experiments confirmed the differential effects and, while each of the compounds increased the initial rate of tubulin polymerization at high concentrations, total tubulin polymer was not enhanced at equilibrium, likely because of the dueling depolymerization effects. Modeling studies predict that the compounds bind to tubulin within the colchicine site and confirm that there are differences in their potential interactions that might underlie their distinct effects on microtubules. Due to their dual properties of microtubule stabilization and destabilization, we propose the name Janus for these compounds after the two-faced Roman god. The identification of synthetically tractable, small molecules that elicit microtubule stabilizing effects is a significant finding with the potential to identify new mechanisms of microtubule stabilization. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

► Show Figures

Graphical abstract

11 pages, 2617 KiB

Open AccessArticle

Activity of Eribulin in a Primary Culture of Well-Differentiated/Dedifferentiated Adipocytic Sarcoma

by Alessandro De Vita, Giacomo Miserocchi, Federica Recine, Laura Mercatali, Federica Pieri, Laura Medri, Alberto Bongiovanni, Davide Cavaliere, Chiara Liverani, Chiara Spadazzi, Dino Amadori and Toni Ibrahim

Molecules 2016, 21(12), 1662; https://doi.org/10.3390/molecules21121662 - 3 Dec 2016

Cited by 22 | Viewed by 5894

Abstract

Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated [...] Read more.

Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated the mechanism of action of this innovative antitubulin agent in well-differentiated/dedifferentiated LPS (ALT/DDLPS) which represents one of the most common adipocytic sarcoma histotypes. A primary culture of ALT/DDLPS from a 54-year-old patient was established. The anticancer activity of eribulin on the patient-derived primary culture was assessed by MTT and tunel assays. Eribulin efficacy was compared to other drugs approved for the treatment of STS. Cell migration and morphology were examined after exposure to eribulin to better understand the drug mechanism of action. Finally, Western blot analysis of apoptosis and migration proteins was performed. The results showed that eribulin exerts its antiproliferative effect by the arrest of cell motility and induction of apoptosis. Our results highlighted the activity of eribulin in the treatment of ALT/DDLPS patients. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

► Show Figures

Figure 1

17 pages, 2164 KiB

Open AccessArticle

Synthesis, Antiphospholipase A₂, Antiprotease, Antibacterial Evaluation and Molecular Docking Analysis of Certain Novel Hydrazones

by Nahed N. E. El-Sayed, Ahmed M. Alafeefy, Mohammed A. Bakht, Vijay H. Masand, Ali Aldalbahi, Nan Chen, Chunhai Fan and Abir Ben Bacha

Molecules 2016, 21(12), 1664; https://doi.org/10.3390/molecules21121664 - 2 Dec 2016

Cited by 17 | Viewed by 14954

Abstract

Some novel hydrazone derivatives 6a–o were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, ¹H-NMR, ¹³C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A₂ (sPLA₂), three [...] Read more.

Some novel hydrazone derivatives 6a–o were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, ¹H-NMR, ¹³C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A₂ (sPLA₂), three protease enzymes and eleven bacterial strains were evaluated. The results revealed that all compounds showed preferential inhibition towards hGIIA isoform of sPLA₂ rather than DrG-IB with compounds 6l and 6e being the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease from Bacillus sp. with compound 6l being the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds; 6a, 6m, and 6o against P. aeruginosa; 6a, 6b, 6d, 6f, 6l, 6m, 6n, and 6o against Serratia; 6k against S. mutans; and compounds 6a, 6d, 6e, 6m, and 6n against E. feacalis. The docking simulations of hydrazones 6a–o with GIIA sPLA₂, proteinase K and hydrazones 6a–e with glutamine-fructose-6-phosphate transaminase were performed to obtain information regarding the mechanism of action. Full article

► Show Figures

Figure 1

8 pages, 558 KiB

Open AccessArticle

Bioactivities of a New Pyrrolidine Alkaloid from the Root Barks of Orixa japonica

by Xin Chao Liu, Daowan Lai, Qi Zhi Liu, Ligang Zhou, Qiyong Liu and Zhi Long Liu

Molecules 2016, 21(12), 1665; https://doi.org/10.3390/molecules21121665 - 2 Dec 2016

Cited by 41 | Viewed by 6623

Abstract

A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against [...] Read more.

A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against the fourth instar larvae of Aedes aegypti (LC₅₀ = 232.09 μg/mL), Anopheles sinensis (LC₅₀ = 49.91 μg/mL), and Culex pipiens pallens (LC₅₀ = 161.10 μg/mL). The new alkaloid also possessed nematicidal activity against Bursaphelenchus xylophilus (LC₅₀ = 391.50 μg/mL) and Meloidogynein congnita (LC₅₀ = 134.51 μg/mL). The results indicate that the crude ethanol extract of O. japonica root barks and its isolated pyrrolidine alkaloid have potential for development into natural larvicides and nematicides. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

► Show Figures

Graphical abstract

18 pages, 2503 KiB

Open AccessArticle

Assessment of the Potential Energy Hypersurfaces in Thymine within Multiconfigurational Theory: CASSCF vs. CASPT2

by Javier Segarra-Martí, Antonio Francés-Monerris, Daniel Roca-Sanjuán and Manuela Merchán

Molecules 2016, 21(12), 1666; https://doi.org/10.3390/molecules21121666 - 3 Dec 2016

Cited by 28 | Viewed by 7226

Abstract

The present study provides new insights into the topography of the potential energy hypersurfaces (PEHs) of the thymine nucleobase in order to rationalize its main ultrafast photochemical decay paths by employing two methodologies based on the complete active space self-consistent field (CASSCF) and [...] Read more.

The present study provides new insights into the topography of the potential energy hypersurfaces (PEHs) of the thymine nucleobase in order to rationalize its main ultrafast photochemical decay paths by employing two methodologies based on the complete active space self-consistent field (CASSCF) and the complete active space second-order perturbation theory (CASPT2) methods: (i) CASSCF optimized structures and energies corrected with the CASPT2 method at the CASSCF geometries and (ii) CASPT2 optimized geometries and energies. A direct comparison between these strategies is drawn, yielding qualitatively similar results within a static framework. A number of analyses are performed to assess the accuracy of these different computational strategies under study based on a variety of numerical thresholds and optimization methods. Several basis sets and active spaces have also been calibrated to understand to what extent they can influence the resulting geometries and subsequent interpretation of the photochemical decay channels. The study shows small discrepancies between CASSCF and CASPT2 PEHs, displaying a shallow planar or twisted ¹(ππ*) minimum, respectively, and thus featuring a qualitatively similar scenario for supporting the ultrafast bi-exponential deactivation registered in thymine upon UV-light exposure. A deeper knowledge of the PEHs at different levels of theory provides useful insight into its correct characterization and subsequent interpretation of the experimental observations. The discrepancies displayed by the different methods studied here are then discussed and framed within their potential consequences in on-the-fly non-adiabatic molecular dynamics simulations, where qualitatively diverse outcomes are expected. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

► Show Figures

Figure 1

14 pages, 2192 KiB

Open AccessArticle

Identification and Characterisation of the Antimicrobial Peptide, Phylloseptin-PT, from the Skin Secretion of Phyllomedusa tarsius, and Comparison of Activity with Designed, Cationicity-Enhanced Analogues and Diastereomers

by Yitian Gao, Di Wu, Xinping Xi, Yue Wu, Chengbang Ma, Mei Zhou, Lei Wang, Mu Yang, Tianbao Chen and Chris Shaw

Molecules 2016, 21(12), 1667; https://doi.org/10.3390/molecules21121667 - 3 Dec 2016

Cited by 35 | Viewed by 7821

Abstract

Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a [...] Read more.

Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a recent study, potent antimicrobial activity was correlated with the conserved structures and cationic amphiphilic characteristics of members of this peptide family. A phylloseptin peptide precursor was discovered here in the skin secretion of Phyllomedusa tarsius and the mature peptide was validated by MS/MS sequencing, and was subsequently named phylloseptin-PT. The chemically-synthesized and purified phylloseptin-PT displayed activity against Staphylococcus aureus and Candida albicans. Nevertheless, a range of cationicity-enhanced peptide analogues of phylloseptin-PT, which contained amino acid substitutions at specific sites, exhibited significant increases in antimicrobial activity compared to native phylloseptin-PT. In addition, alternative conformers which were designed and chemically-synthesized with d-lysine, showed potent antimicrobial activity and enhanced bioavailability. These data indicate that phylloseptins may represent potential candidates for next-generation antibiotics. Thus, rational design through modification of natural antimicrobial peptide templates could provide an accelerated path to overcoming obstacles en-route to their possible clinical applications. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

► Show Figures

Figure 1

11 pages, 1235 KiB

Open AccessArticle

Xanthines Studied via Femtosecond Fluorescence Spectroscopy

by Pascale Changenet-Barret, Lajos Kovács, Dimitra Markovitsi and Thomas Gustavsson

Molecules 2016, 21(12), 1668; https://doi.org/10.3390/molecules21121668 - 3 Dec 2016

Cited by 9 | Viewed by 8044

Abstract

Xanthines represent a wide class of compounds closely related to the DNA bases adenine and guanine. Ubiquitous in the human body, they are capable of replacing natural bases in double helices and give rise to four-stranded structures. Although the use of their fluorescence [...] Read more.

Xanthines represent a wide class of compounds closely related to the DNA bases adenine and guanine. Ubiquitous in the human body, they are capable of replacing natural bases in double helices and give rise to four-stranded structures. Although the use of their fluorescence for analytical purposes was proposed, their fluorescence properties have not been properly characterized so far. The present paper reports the first fluorescence study of xanthine solutions relying on femtosecond spectroscopy. Initially, we focus on 3-methylxanthine, showing that this compound exhibits non-exponential fluorescence decays with no significant dependence on the emission wavelength. The fluorescence quantum yield (3 × 10⁻⁴) and average decay time (0.9 ps) are slightly larger than those found for the DNA bases. Subsequently, we compare the dynamical fluorescence properties of seven mono-, di- and tri-methylated derivatives. Both the fluorescence decays and fluorescence anisotropies vary only weakly with the site and the degree of methylation. These findings are in line with theoretical predictions suggesting the involvement of several conical intersections in the relaxation of the lowest singlet excited state. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

► Show Figures

Graphical abstract

22 pages, 11937 KiB

Open AccessArticle

Decomposition of Intermolecular Interactions in the Crystal Structure of Some Diacetyl Platinum(II) Complexes: Combined Hirshfeld, AIM, and NBO Analyses

by Saied M. Soliman and Assem Barakat

Molecules 2016, 21(12), 1669; https://doi.org/10.3390/molecules21121669 - 6 Dec 2016

Cited by 16 | Viewed by 5017

Abstract

Intermolecular interactions play a vital role in crystal structures. Therefore, we conducted a topological study, using Hirshfeld surfaces and atom in molecules (AIM) analysis, to decompose and analyze, respectively, the different intermolecular interactions in six hydrazone-diacetyl platinum(II) complexes. Using AIM and natural bond [...] Read more.

Intermolecular interactions play a vital role in crystal structures. Therefore, we conducted a topological study, using Hirshfeld surfaces and atom in molecules (AIM) analysis, to decompose and analyze, respectively, the different intermolecular interactions in six hydrazone-diacetyl platinum(II) complexes. Using AIM and natural bond orbital (NBO) analyses, we determined the type, nature, and strength of the interactions. All the studied complexes contain C-H⋯O interactions, and the presence of bond critical points along the intermolecular paths underlines their significance. The electron densities (ρ(r)) at the bond critical points (0.0031–0.0156 e/a₀³) fall within the typical range for H-bonding interactions. Also, the positive values of the Laplacian of the electron density (∇²ρ(r)) revealed the depletion of electronic charge on the interatomic path, another characteristic feature of closed-shell interactions. The ratios of the absolute potential energy density to the kinetic energy density (|V(r)|/G(r)) and ρ(r) are highest for the O2⋯H15-N3 interaction in [Pt(COMe)₂(2-pyCMe=NNH₂)] (1); hence, this interaction has the highest covalent character of all the O⋯H intermolecular interactions. Interestingly, in [Pt(COMe)₂(H₂NN=CMe-CMe=NNH₂)] (3), there are significant N-H⋯Pt interactions. Using the NBO method, the second-order interaction energies, E⁽²⁾, of these interactions range from 3.894 to 4.061 kJ/mol. Furthermore, the hybrid Pt orbitals involved in these interactions are comprised of d_xy, d_xz, and s atomic orbitals. Full article

► Show Figures

Graphical abstract

11 pages, 8240 KiB

Open AccessArticle

Clarification of the Antagonistic Effect of the Lipopeptides Produced by Bacillus amyloliquefaciens BPD1 against Pyricularia oryzae via In Situ MALDI-TOF IMS Analysis

by Jen-Hung Liao, Pi-Yu Chen, Yu-Liang Yang, Shu-Chen Kan, Feng-Chia Hsieh and Yung-Chang Liu

Molecules 2016, 21(12), 1670; https://doi.org/10.3390/molecules21121670 - 3 Dec 2016

Cited by 38 | Viewed by 7972

Abstract

This study tried to clarify the antagonistic effect of the lipopeptides secreted by Bacillus amyloliquefaciens strain BPD1 (Ba-BPD1) against Pyricularia oryzae Cavara (PO). To determine the major antifungal lipopeptides effective against PO, single and dual cultures were carried out in solid-state media. The [...] Read more.

This study tried to clarify the antagonistic effect of the lipopeptides secreted by Bacillus amyloliquefaciens strain BPD1 (Ba-BPD1) against Pyricularia oryzae Cavara (PO). To determine the major antifungal lipopeptides effective against PO, single and dual cultures were carried out in solid-state media. The matrix-assisted laser desorption/ionization–time of flight imaging mass spectrometry (MALDI-TOF IMS) was used to identify the most effective lipopeptide in situ. Meanwhile, the morphology of pathogen fungi treated with lipopeptides was observed via the SEM. Of the three lipopeptide families, surfactin, iturin, and fengycin, the last was identified as the most effective for inhibiting mycelium growth and conidial germination of PO. The conidia and hyphae of fengycin-treated PO were shown to become deformed and tumorous under exposure. This study provides insights into the antagonistic effect of Ba-BPD1 against fungal phytopathogens. Such insights are helpful in the development of reagents for biological control applications. Full article

(This article belongs to the Section Metabolites)

► Show Figures

Figure 1

20 pages, 3789 KiB

Open AccessArticle

Extraction and Quantification of Bioactive Tyrian Purple Precursors: A Comparative and Validation Study from the Hypobranchial Gland of a Muricid Dicathais orbita

by Roselyn Valles-Regino, Peter Mouatt, David Rudd, Lachlan H. Yee and Kirsten Benkendorff

Molecules 2016, 21(12), 1672; https://doi.org/10.3390/molecules21121672 - 5 Dec 2016

Cited by 13 | Viewed by 6620

Abstract

Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass [...] Read more.

Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass spectrometry (HPLC-MS) with diode array detector (DAD). Quantification of the dominant secondary metabolites from D. orbita is described, followed by a comparison of solvent extraction procedures and stability studies. The intra- and inter-day relative standard deviation (RSD) for tyrindoxyl sulphate was 0.46% and 0.17%, respectively. The quantification was linear for standards murexine, 6-bromoisatin, and tyrindoxyl sulphate. The limits of detection were 0.03, 0.004, and 0.07 mg/mL, respectively, and the limits of quantification were 0.09, 0.01, and 0.22 mg/mL, respectively. The results showed that alcoholic solvents were better for extracting choline ester and indoxyl sulphate ultimate precursors, while chloroform was more suitable for the extraction of the intermediate precursors. Multivariate analysis revealed significant differences in extract composition according to the solvent used. Stability testing showed an increase of the oxidative compounds 6-bromoisatin and putative tyrindoxyl S-oxide sulphate in the ethanol extracts while more degradation products were seen in the chloroform extracts after months of cold storage. The validated method was found to be simple, reproducible, precise, and suitable for quantification of the secondary metabolites of muricid molluscs for dye precursor and nutraceutical quality control, as well as applications in marine chemical ecology. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

► Show Figures

Graphical abstract

13 pages, 1483 KiB

Open AccessArticle

Using Light Microscopy and Liquid Chromatography Tandem Mass Spectrometry for Qualitative and Quantitative Control of a Combined Three-Herb Formulation in Different Preparations

by Tun-Pin Hsueh, Wan-Ling Lin and Tung-Hu Tsai

Molecules 2016, 21(12), 1673; https://doi.org/10.3390/molecules21121673 - 6 Dec 2016

Cited by 7 | Viewed by 5906

Abstract

Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the [...] Read more.

Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the quality and quantity of an herbal formulation (Chinese name: Yin-Chen-Hao-Tang) using physical and chemical examinations. Physical examination of Yin-Chen-Hao-Tang in pharmaceutical herbal products, raw fiber powders, and decoction preparations was performed using Congo red and iodine-potassium staining. A sensitive and validated method employing ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed to simultaneously quantify the bioactive compounds scoparone, geniposide, and rhein in the Yin-Chen-Hao-Tang formulation in different preparations. Physical examination indicated that cellulose fibers with irregular round shapes were present in the pharmaceutical herbal products. The developed UHPLC-MS/MS method showed good linearity and was well validated. The quantification results revealed that the decoction preparations had the highest amounts of geniposide and rhein. Scoparone appeared in pharmaceutical herbal products from two manufacturers. This experiment provides a qualitative and quantitative method using physical and chemical examinations to test different preparations of herbal products. The results provide a reference for clinical herbal product preparations and further pharmacokinetic research. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Figure 1

10 pages, 3929 KiB

Open AccessArticle

Synthesis and Antitumor Activity of 5-Bromo-7-azaindolin-2-one Derivatives Containing a 2,4-Dimethyl-1H-pyrrole-3-carboxamide Moiety

by Jun Zhang, Weiyi Shen, Xiaoning Li, Yun Chai, Senjun Li, Kai Lv, Huiyuan Guo and Mingliang Liu

Molecules 2016, 21(12), 1674; https://doi.org/10.3390/molecules21121674 - 6 Dec 2016

Cited by 9 | Viewed by 4681

Abstract

We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds [...] Read more.

We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds exhibit broad-spectrum antitumor potency, and the most active compound 23p (IC₅₀: 2.357–3.012 μM) was found more potent than Sunitinib (IC₅₀: 31.594–49.036 μM) against HepG2, A549 and Skov-3, respectively. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

10 pages, 772 KiB

Open AccessArticle

Subcritical Butane Extraction of Wheat Germ Oil and Its Deacidification by Molecular Distillation

by Jinwei Li, Dewei Sun, Lige Qian and Yuanfa Liu

Molecules 2016, 21(12), 1675; https://doi.org/10.3390/molecules21121675 - 7 Dec 2016

Cited by 21 | Viewed by 6549

Abstract

Extraction and deacidification are important stages for wheat germ oil (WGO) production. Crude WGO was extracted using subcritical butane extraction (SBE) and compared with traditional solvent extraction (SE) and supercritical carbon dioxide extraction (SCE) based on the yield, chemical index and fatty acid [...] Read more.

Extraction and deacidification are important stages for wheat germ oil (WGO) production. Crude WGO was extracted using subcritical butane extraction (SBE) and compared with traditional solvent extraction (SE) and supercritical carbon dioxide extraction (SCE) based on the yield, chemical index and fatty acid profile. Furthermore, the effects of the molecular distillation temperature on the quality of WGO were also investigated in this study. Results indicated that WGO extracted by SBE has a higher yield of 9.10% and better quality; at the same time, its fatty acid composition has no significant difference compared with that of SE and SCE. The molecular distillation experiment showed that the acid value, peroxide value and p-anisidine value of WGO were reduced with the increase of the evaporation temperatures, and the contents of the active constituents of tocopherol, polyphenols and phytosterols are simultaneously decreased. Generally, the distillation temperature of 150 °C is an appropriate condition for WGO deacidification with the higher deacidification efficiency of 77.78% and the higher retention rate of active constituents. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

► Show Figures

Figure 1

16 pages, 11365 KiB

Open AccessArticle

The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy

by Shun-Ting Chen, Tzung-Yan Lee, Tung-Hu Tsai, Yin-Cheng Lin, Chin-Ping Lin, Hui-Ru Shieh, Ming-Ling Hsu, Chih-Wen Chi, Ming-Cheng Lee, Hen-Hong Chang and Yu-Jen Chen

Molecules 2016, 21(12), 1677; https://doi.org/10.3390/molecules21121677 - 6 Dec 2016

Cited by 37 | Viewed by 6542

Abstract

Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells [...] Read more.

Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibits growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells, and may have potential as a chemotherapy or radiotherapy sensitizer in colorectal cancer treatment. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

► Show Figures

Figure 1

12 pages, 3968 KiB

Open AccessArticle

Virtual-Wall Model for Molecular Dynamics Simulation

by Lijuan Qian, Chengxu Tu, Fubing Bao and Yonghao Zhang

Molecules 2016, 21(12), 1678; https://doi.org/10.3390/molecules21121678 - 9 Dec 2016

Cited by 8 | Viewed by 5562

Abstract

A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the [...] Read more.

A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the atomic wall causes the periodicity of the force acting on a fluid molecule from the wall molecules. This force is first calculated and then stored in the memory. A fluid molecule appearing in the wall force field is subjected to the force from the wall molecules. The force can then be determined by the position of the molecule relative to the wall. This model avoids excessive calculations of fluid-wall interactions and reduces the computational time drastically. The time reduction is significant for small fluid density and channel height. The virtual-wall model is applied to Poiseuille and Couette flows, and to a flow in a channel with a rough surface. Results of the virtual and atomic wall simulations agree well with each other, thereby indicating the usefulness of the virtual-wall model. The appropriate bin size and cut-off radius in the virtual-wall model are also discussed. Full article

► Show Figures

Figure 1

12 pages, 5709 KiB

Open AccessArticle

Design of Heterogeneous Hoveyda–Grubbs Second-Generation Catalyst–Lipase Conjugates

by Anthony Neville, Javier Iniesta and Jose M. Palomo

Molecules 2016, 21(12), 1680; https://doi.org/10.3390/molecules21121680 - 6 Dec 2016

Cited by 8 | Viewed by 7016

Abstract

Heterogeneous catalysts have been synthesized by the conjugation of Hoveyda–Grubbs second-generation catalyst with a lipase. The catalytic properties of the organometallic compound in solution were firstly optimized, evaluating the activity of Ru in the ring-closing metathesis of diethyldiallymalonate at 25 °C at different [...] Read more.

Heterogeneous catalysts have been synthesized by the conjugation of Hoveyda–Grubbs second-generation catalyst with a lipase. The catalytic properties of the organometallic compound in solution were firstly optimized, evaluating the activity of Ru in the ring-closing metathesis of diethyldiallymalonate at 25 °C at different solvents and in the presence of different additives. The best result was found using tetrahydrofuran as a solvent. Some additives such as phenylboronic acid or polyetheneglycol slightly improved the activity of the Ru catalyst whereas others, such as pyridine or dipeptides affected it negatively. The organometallic compound immobilized on functionalized-surface materials activated with boronic acid or epoxy groups (around 50–60 µg per mg support) and showed 50% conversion at 24 h in the ring-closing metathesis. Cross-linked enzyme aggregates (CLEA’s) of the Hoveyda–Grubbs second-generation catalyst with Candida antarctica lipase (CAL-B) were prepared, although low Ru catalyst was found to be translated in low conversion. Therefore, a sol–gel preparation of the Hoveyda–Grubbs second-generation and CAL-B was performed. This catalyst exhibited good activity in the metathesis of diethyldiallymalonate in toluene and in aqueous media. Finally, a new sustainable approach was used by the conjugation lipase–Grubbs in solid phase in aqueous media. Two strategies were used: one using lipase previously covalently immobilized on an epoxy-Sepharose support (hydrophilic matrix) and then conjugated with grubbs; and in the second, the free lipase was incubated with organometallic in aqueous solution and then immobilized on epoxy-Sepharose. The different catalysts showed excellent conversion values in the ring-closing metathesis of diethyldiallymalonate in aqueous media at 25 °C. Full article

(This article belongs to the Special Issue Biomolecules Modification)

► Show Figures

Figure 1

12 pages, 2109 KiB

Open AccessArticle

Pentacoordinate and Hexacoordinate Mn(III) Complexes of Tetradentate Schiff-Base Ligands Containing Tetracyanidoplatinate(II) Bridges and Revealing Uniaxial Magnetic Anisotropy

by Ivan Nemec, Radovan Herchel and Zdeněk Trávníček

Molecules 2016, 21(12), 1681; https://doi.org/10.3390/molecules21121681 - 8 Dec 2016

Cited by 13 | Viewed by 5970

Abstract

Crystal structures and magnetic properties of polymeric and trinuclear heterobimetallic Mn^III···Pt^II···Mn^III coordination compounds, prepared from the Ba[Pt(CN)₄] and [Mn(L4A/B)(Cl)] (1a/b) precursor complexes, are reported. The polymeric complex [{Mn(L4A)}₂{μ⁴-Pt(CN) [...] Read more.

Crystal structures and magnetic properties of polymeric and trinuclear heterobimetallic Mn^III···Pt^II···Mn^III coordination compounds, prepared from the Ba[Pt(CN)₄] and [Mn(L4A/B)(Cl)] (1a/b) precursor complexes, are reported. The polymeric complex [{Mn(L4A)}₂{μ⁴-Pt(CN)₄}]_n (2a), where H₂L4A = N,N’-ethylene-bis(salicylideneiminate), comprises the {Mn(L4A)} moieties covalently connected through the [Pt(CN)₄]²⁻ bridges, thus forming a square-grid polymeric structure with the hexacoordinate Mn^III atoms. The trinuclear complex [{Mn(L4B)}₂{μ-Pt(CN)₄}] (2b), where H₂L4B = N,N’-benzene-bis(4-aminodiethylene-salicylideneiminate), consists of two [{Mn(L4B)} moieties, involving pentacoordinate Mn^III atoms, bridged through the tetracyanidoplatinate (II) bridges to which they are coordinated in a trans fashion. Both complexes possess uniaxial type of magnetic anisotropy, with D (the axial parameter of zero-field splitting) = −3.7(1) in 2a and −2.2(1) cm⁻¹ in 2b. Furthermore, the parameters of magnetic anisotropy 2a and 2b were also thoroughly studied by theoretical complete active space self-consistent field (CASSCF) methods, which revealed that the former is much more sensitive to the ligand field strength of the axial ligands. Full article

(This article belongs to the Section Organometallic Chemistry)

► Show Figures

Figure 1

13 pages, 748 KiB

Open AccessCommunication

Synthesis and Determination of Physicochemical Properties of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Alkoxyethoxybenzoates

by Pavlina Marvanova, Tereza Padrtova, Klara Odehnalova, Ondrej Hosik, Michal Oravec and Petr Mokry

Molecules 2016, 21(12), 1682; https://doi.org/10.3390/molecules21121682 - 7 Dec 2016

Cited by 5 | Viewed by 5942

Abstract

Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log k_w) and dissociation constant (pK_a) were experimentally determined and compared to the software calculated data. The lipophilicity index was [...] Read more.

Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log k_w) and dissociation constant (pK_a) were experimentally determined and compared to the software calculated data. The lipophilicity index was determined by means of reversed-phase high performance liquid chromatography (RP-HPLC). The pK_a values were determined by means of capillary zone electrophoresis. The “drug-likeness” properties according to the Lipinski Rule of Five and prediction of possible blood–brain barrier penetration were computed and discussed. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

► Show Figures

Scheme 1

9 pages, 2077 KiB

Open AccessArticle

Stereoselective Fluorescence Quenching in the Electron Transfer Photooxidation of Nucleobase-Related Azetidines by Cyanoaromatics

by Ana B. Fraga-Timiraos, Gemma M. Rodríguez-Muñiz, Vicente Peiro-Penalba, Miguel A. Miranda and Virginie Lhiaubet-Vallet

Molecules 2016, 21(12), 1683; https://doi.org/10.3390/molecules21121683 - 7 Dec 2016

Cited by 6 | Viewed by 5226

Abstract

Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in [...] Read more.

Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in the repair of DNA (6-4) photoproduct by photolyase. In this context, we examine here the redox properties of the two azetidine isomers obtained from photocycloaddition between 6-aza-1,3-dimethyluracil and cyclohexene. Steady-state and time-resolved fluorescence experiments using a series of photoreductants and photooxidants have been run to evaluate the efficiency of the electron transfer process. Analysis of the obtained quenching kinetics shows that the azetidine compounds can act as electron donors. Additionally, it appears that the cis isomer is more easily oxidized than its trans counterpart. This result is in agreement with electrochemical studies performed on both azetidine derivatives. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

► Show Figures

Figure 1

11 pages, 4293 KiB

Open AccessCommunication

Design, Synthesis, and Biological Evaluation of Novel Benzofuran Derivatives Bearing N-Aryl Piperazine Moiety

by Yulu Ma, Xi Zheng, Hui Gao, Chunping Wan, Gaoxiong Rao and Zewei Mao

Molecules 2016, 21(12), 1684; https://doi.org/10.3390/molecules21121684 - 9 Dec 2016

Cited by 41 | Viewed by 6886

Abstract

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16 [...] Read more.

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16 not only had inhibitory effect on the generation of NO (IC₅₀ = 5.28 μM), but also showed satisfactory and selective cytotoxic activity against human lung cancer line (A549) and gastric cancer cell (SGC7901) (IC₅₀ = 0.12 μM and 2.75 μM, respectively), which was identified as the most potent anti-inflammatory and anti-tumor agent in this study. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Scheme 1

14 pages, 2790 KiB

Open AccessArticle

Geometry Constrained N-(5,6,7-Trihydroquinolin-8-ylidene)arylaminopalladium Dichloride Complexes: Catalytic Behavior toward Methyl Acrylate (MA), Methyl Acrylate-co-Norbornene (MA-co-NB) Polymerization and Heck Coupling

by Yanning Zeng, Qaiser Mahmood, Tongling Liang and Wen-Hua Sun

Molecules 2016, 21(12), 1686; https://doi.org/10.3390/molecules21121686 - 7 Dec 2016

Cited by 13 | Viewed by 5846

Abstract

A new pair of plladium complexes (Pd4 and Pd5) ligated with constrained N-(5,6,7-trihydroquinolin-8-ylidene)arylamine ligands have been prepared and well characterized by ¹H-, ¹³C-NMR and FTIR spectroscopies as well as elemental analysis. The molecular structure of Pd4 and Pd5 [...] Read more.

A new pair of plladium complexes (Pd4 and Pd5) ligated with constrained N-(5,6,7-trihydroquinolin-8-ylidene)arylamine ligands have been prepared and well characterized by ¹H-, ¹³C-NMR and FTIR spectroscopies as well as elemental analysis. The molecular structure of Pd4 and Pd5 in solid state have also been determined by X-ray diffraction, showing slightly distorted square planar geometry around the palladium metal center. All complexes Pd1–Pd5 are revealed highly efficient catalyst in methyl acrylate (MA) polymerization as well as methyl acrylate/norbornene (MA/NB) copolymerization. In the case of MA polymerization, as high as 98.4% conversion with high molecular weight up to 6282 kg·mol⁻¹ was achieved. Likewise, Pd3 complex has good capability to incorporate about 18% NB content into MA polymer chains. Furthermore, low catalyst loadings (0.002 mol %) of Pd4 or Pd5 are able to efficiently mediate the coupling of haloarenes with styrene affording up to 98% conversion. Full article

(This article belongs to the Special Issue Palladium Catalysts 2016)

► Show Figures

Graphical abstract

15 pages, 1755 KiB

Open AccessArticle

The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice

by Miao Long, Shuhua Yang, Yuan Wang, Peng Li, Yi Zhang, Shuang Dong, Xinliang Chen, Jiayi Guo, Jianbin He, Zenggui Gao and Jun Wang

Molecules 2016, 21(12), 1687; https://doi.org/10.3390/molecules21121687 - 7 Dec 2016

Cited by 39 | Viewed by 6838

Abstract

This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of [...] Read more.

This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of 40 mg/kg body mass (B.M.) ZEN for 28 days. Then, interventions with different doses (0.1, 0.2, and 0.4 mg/kg B.M.) of Se were conducted on mice to analyse the changes in organ indexes of epididymis and testis, antioxidant capability of testis, serum level of testosterone, sperm concentration and motility parameters, and the expression levels of apoptosis-associated genes and blood testis barrier- (BTB) related genes. Our results showed that Se could greatly improve the ZEN-induced decrease of epididymis indexes and testis indexes. Results also showed that the decrease in sperm concentration, sperm normality rate, and sperm motility parameters, including percentage of motile sperm (motile), tropism percentage (progressive) and sperm average path velocity (VAP), caused by ZEN were elevated upon administration of the higher dose (0.4 mg/kg) and intermediate dose (0.2 mg/kg) of Se. Selenium also significantly reduced the content of malondialdehyde (MDA) but enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the testis tissue. Further research demonstrated that ZEN increased the level of mRNA expression of BCL2-associated X protein (Bax) and caspase 3 (Casp3), decreased the level of mRNA expression of B cell leukemia/lymphoma 2 (Bcl2), vimentin (Vim) and cadherin 2 (Cdh2), whereas the co-administration of Se reversed these gene expression levels. Our results indicated that high levels of Se could protect against reproductive system damage in male mice caused by ZEN and the mechanism might such be that Se improved mice antioxidant ability, inhibited reproductive cell apoptosis, and increased the decrease of BTB integrity-related genes caused by ZEN. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

► Show Figures

Figure 1

13 pages, 635 KiB

Open AccessArticle

Impact of Cluster Zone Leaf Removal on Grapes cv. Regent Polyphenol Content by the UPLC-PDA/MS Method

by Kamila Mijowska, Ireneusz Ochmian and Jan Oszmiański

Molecules 2016, 21(12), 1688; https://doi.org/10.3390/molecules21121688 - 11 Dec 2016

Cited by 29 | Viewed by 6384

Abstract

Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal [...] Read more.

Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal techniques adequate for the particular climate conditions of a vineyard area. Defoliation experiments on vine cv. Regent were conducted in two consecutive years (2014 and 2015). The effect of leaf removal treatment on the qualitative and quantitative composition of the polyphenol compounds in the grapes, with reference to the basic weather conditions of the vineyard area, located in Szczecin in the North-Western part of Poland, was assessed. Defoliation was performed manually in the cluster zone at three phenological plant stages: pre-flowering, berry-set and véraison. Leaf removal, especially early defoliation (pre-flowering), enhanced total polyphenol content, including the amount of anthocyanins, flavonols and flavan-3-ols and furthermore, it increased the amount of soluble solids, decreasing the titratable acidity in grapes. On the other hand, the treatments had a reducing impact on the phenolic acids in berries. Defoliation at earlier stages of cluster development appears to be an efficient strategy for improving berry quality in cool climate areas, however, additionally further weather data control is required to determine the effects on berry components. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Figure 1

12 pages, 2696 KiB

Open AccessArticle

Methotrexate and Cytarabine—Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study

by Danuta Pentak, Violetta Kozik, Andrzej Bąk, Paulina Dybał, Aleksander Sochanik and Josef Jampilek

Molecules 2016, 21(12), 1689; https://doi.org/10.3390/molecules21121689 - 8 Dec 2016

Cited by 26 | Viewed by 6624

Abstract

Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The [...] Read more.

Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC) interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance_2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR) were consistent with the results obtained by Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR). Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

► Show Figures

Figure 1

11 pages, 14718 KiB

Open AccessArticle

Metal-Free Photoredox Catalyzed Cyclization of O-(2,4-Dinitrophenyl)oximes to Phenanthridines

by Xiubin Liu, Zhixing Qing, Pi Cheng, Xinyu Zheng, Jianguo Zeng and Hongqi Xie

Molecules 2016, 21(12), 1690; https://doi.org/10.3390/molecules21121690 - 8 Dec 2016

Cited by 30 | Viewed by 5818

Abstract

A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr₂NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl [...] Read more.

A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr₂NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl radical intermediates by single-electron reduction, which then underwent intermolecular homolytic aromatic substitution (HAS) reactions to give phenanthridine derivatives. Full article

(This article belongs to the Section Photochemistry)

► Show Figures

Graphical abstract

11 pages, 3373 KiB

Open AccessArticle

Extract of Monascus purpureus CWT715 Fermented from Sorghum Liquor Biowaste Inhibits Migration and Invasion of SK-Hep-1 Human Hepatocarcinoma Cells

by Wen-Teish Chang, Cheng-Hung Chuang, Wan-Ju Lee and Chin-Shiu Huang

Molecules 2016, 21(12), 1691; https://doi.org/10.3390/molecules21121691 - 8 Dec 2016

Cited by 13 | Viewed by 5553

Abstract

Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP) fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma [...] Read more.

Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP) fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma SK-Hep-1 cells. Kinmen sorghum liquor waste was used as the primary nutrient source to produce metabolites (including pigments) of MP. In the presence of 10 µg/mL MP-fermented broth (MFB), the anti-invasive activity increased with increasing fermentation time reaching a maximum at six days of fermentation. Interestingly, MFB also produced maximal pigment content at six days. Treatment for 24 h with MFB (10–100 µg/mL) obtained from fermentation for six days significantly inhibited cell migration and invasion, and these effects were concentration-dependent. MFB also significantly enhanced nm23-H1 protein expression in a concentration-dependent manner, which was highly correlated with migration and invasion. These results suggest that MFB has significant anti-migration and anti-invasion activities and that these effects are associated with the induction of nm23-H1 protein expression. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

► Show Figures

Graphical abstract

8 pages, 381 KiB

Open AccessArticle

Bioassay-Guided Isolation of Cytotoxic Isocryptoporic Acids from Cryptoporus volvatus

by Ling-Yun Zhou, Xiao-Hong Yu, Bin Lu and Yan Hua

Molecules 2016, 21(12), 1692; https://doi.org/10.3390/molecules21121692 - 8 Dec 2016

Cited by 9 | Viewed by 3933

Abstract

The present work constitutes a contribution to the phytochemical investigation of Cryptoporus volvatus aiming to search for effective cytotoxic constituents against tumor cell lines in vivo. Bioassay-guided separation of the ethylacetate extract of C. volvatus afforded four new isocryptoporic acid (ICA) derivatives, ICA-B [...] Read more.

The present work constitutes a contribution to the phytochemical investigation of Cryptoporus volvatus aiming to search for effective cytotoxic constituents against tumor cell lines in vivo. Bioassay-guided separation of the ethylacetate extract of C. volvatus afforded four new isocryptoporic acid (ICA) derivatives, ICA-B trimethyl ester (1), ICA-E (2), ICA-E pentamethyl ester (3), and ICA-G (4), together with nine known cryptoporic acids. These isocryptoporic acids are isomers of the cryptoporic acids with drimenol instead of albicanol as the terpenoid fragment; their structures were elucidated on the basis of spectroscopic evidences (UV, IR, HRMS, and NMR) and comparison with literature values. All isolates show certain cytotoxic activities against five tumor cell lines. Among them, compound 4 showed an comparable activity to that of the positive control cis-platin, while other compounds exhibited weak cytotoxic activities. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

15 pages, 2396 KiB

Open AccessArticle

Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia

by Huiqiang Wei, Deguan Li, Xiangbo Yang, Haihua Shang, Saijun Fan, Yiliang Li and Dan Song

Molecules 2016, 21(12), 1693; https://doi.org/10.3390/molecules21121693 - 14 Dec 2016

Cited by 12 | Viewed by 7294

Abstract

Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16a–p)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of [...] Read more.

Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16a–p)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia. Meanwhile, several of the above compounds demonstrated better bioactivity than vandetanib in VEGF gene expression inhibition. Owing to the excellent IC₅₀ value (1.64 μmol/L), the inhibition ratios of 16f over A549 and H446 cells were 62.01% and 59.86% at the concentration of 0.5 μM in hypoxia, respectively. All of these results indicated that 16f was a potential cancer therapeutic agent in hypoxia and was worthy of further development. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

14 pages, 1355 KiB

Open AccessArticle

Polyphenols Isolated from Xanthoceras sorbifolia Husks and Their Anti-Tumor and Radical-Scavenging Activities

by Chun-Yan Yang, Wei Ha, Yong Lin, Kan Jiang, Jun-Li Yang and Yan-Ping Shi

Molecules 2016, 21(12), 1694; https://doi.org/10.3390/molecules21121694 - 9 Dec 2016

Cited by 33 | Viewed by 5920

Abstract

Xanthoceras sorbifolia Bunge. is used in traditional medicine in North China. To evaluate the anti-tumor and radical-scavenging activities of X. sorbifolia husks polyphenols and determine their structure-activity relationships, 37 polyphenols 1–37 were obtained by bioassay-guided fractionation. Two new compounds 1– [...] Read more.

Xanthoceras sorbifolia Bunge. is used in traditional medicine in North China. To evaluate the anti-tumor and radical-scavenging activities of X. sorbifolia husks polyphenols and determine their structure-activity relationships, 37 polyphenols 1–37 were obtained by bioassay-guided fractionation. Two new compounds 1–2, and compounds 5, 6, 8, 9, 11, 14–17, 21–25, 27–29, 31, 33, 34, 36, and 37 were isolated from the genus Xanthoceras for the first time. Compounds 1–37 did not show strong cytotoxicity against the four tested tumor cell lines (A549, HepG2, MGC-803, and MFC) compared to paclitaxel and under the conditions tested in the anti-tumor assay, but compounds 3, 4, 7, 8, 10, 18–20, 25, 26, 29, 30, 32, and 35 exhibited stronger radical-scavenging activity than ascorbic acid in a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assay. This was the first report on the anti-tumor and radical-scavenging activities of the polyphenols isolated from X. sorbifolia husks. Overall, the present study contributed valuable information concerning X. sorbifolia husks use in medicine and pharmacology. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

► Show Figures

Graphical abstract

11 pages, 2353 KiB

Open AccessArticle

Optimized and Automated Radiosynthesis of [¹⁸F]DHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography

by Wenjie Zhang, Zhengxin Cai, Lin Li, Jim Ropchan, Keunpoong Lim, Nabil E. Boutagy, Jing Wu, John C. Stendahl, Wenhua Chu, Robert Gropler, Albert J. Sinusas, Chi Liu and Yiyun Huang

Molecules 2016, 21(12), 1696; https://doi.org/10.3390/molecules21121696 - 9 Dec 2016

Cited by 20 | Viewed by 5998

Abstract

Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these [...] Read more.

Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [¹⁸F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([¹⁸F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [¹⁸F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/µmol (n = 2). Fully automated radiosynthesis of [¹⁸F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/µmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[¹⁸F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [¹⁸F]DHMT was successfully tested for PET imaging in a healthy beagle dog. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

► Show Figures

Figure 1

17 pages, 5544 KiB

Open AccessArticle

Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions

by Xiaoguang Zhang, Peiye Liu and Lei Zhu

Molecules 2016, 21(12), 1697; https://doi.org/10.3390/molecules21121697 - 9 Dec 2016

Cited by 22 | Viewed by 8507

Abstract

This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work, [...] Read more.

This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II)- (via an induction period) and copper(I)-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethyl)propargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II)- and copper(I)-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained. Full article

(This article belongs to the Special Issue Recent Advances in CuAAC Click Chemistry)

► Show Figures

Figure 1

12 pages, 543 KiB

Open AccessArticle

Evaluation of Chemical Composition and Antileishmanial and Antituberculosis Activities of Essential Oils of Piper Species

by Karine Zanoli Bernuci, Camila Cristina Iwanaga, Carla Maria Mariano Fernandez-Andrade, Fabiana Brusco Lorenzetti, Eduardo Caio Torres-Santos, Viviane Dos Santos Faiões, José Eduardo Gonçalves, Wanderlei Do Amaral, Cícero Deschamps, Regiane Bertin de Lima Scodro, Rosilene Fressatti Cardoso, Vanessa Pietrowski Baldin and Diógenes Aparício Garcia Cortez

Molecules 2016, 21(12), 1698; https://doi.org/10.3390/molecules21121698 - 12 Dec 2016

Cited by 59 | Viewed by 7875

Abstract

Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC–MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority [...] Read more.

Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC–MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC₅₀) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H₃₇Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

► Show Figures

Figure 1

12 pages, 4284 KiB

Open AccessArticle

Photostability and Performance of Polystyrene Films Containing 1,2,4-Triazole-3-thiol Ring System Schiff Bases

by Gassan Q. Ali, Gamal A. El-Hiti, Ivan Hameed R. Tomi, Raghad Haddad, Alaa J. Al-Qaisi and Emad Yousif

Molecules 2016, 21(12), 1699; https://doi.org/10.3390/molecules21121699 - 9 Dec 2016

Cited by 52 | Viewed by 6302

Abstract

Series of 4-(4-substituted benzylideneamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiols were synthesized and their structures were confirmed. The synthesized Schiff bases were used as photostabilizers for polystyrene against photodegradation. Polystyrene polymeric films containing synthesized Schiff bases (0.5% by weight) were irradiated (λ_max = 365 nm and [...] Read more.

Series of 4-(4-substituted benzylideneamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiols were synthesized and their structures were confirmed. The synthesized Schiff bases were used as photostabilizers for polystyrene against photodegradation. Polystyrene polymeric films containing synthesized Schiff bases (0.5% by weight) were irradiated (λ_max = 365 nm and light intensity = 6.43 × 10⁻⁹ ein·dm⁻³·s⁻¹) at room temperature. The photostabilization effect of 1,2,4-triazole-3-thiols Schiff bases was determined using various methods. All the additives used enhanced the photostability of polystyrene films against irradiation compared with the result obtained in the absence of Schiff base. The Schiff bases can act as photostabilizers for polystyrene through the direct absorption of UV radiation and/or radical scavengers. Full article

► Show Figures

Graphical abstract

8 pages, 942 KiB

Open AccessArticle

Six New Triterpene Derivatives from Aralia chinensis Var. dasyphylloides

by Rui-xi Gao, Maochuan Liao, Xianju Huang, Yu Chen, Guangzhong Yang and Jun Li

Molecules 2016, 21(12), 1700; https://doi.org/10.3390/molecules21121700 - 9 Dec 2016

Cited by 7 | Viewed by 5227

Abstract

Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives ( [...] Read more.

Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives (1–6), together with two known compounds were isolated from the barks of A. chinensis var. dasyphylloides. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and chemical methods. They were identified as 3-oxo-oleana-11,13(18)-dien-28,30-dioic acid (1), 30-hydroxy-3-oxo-oleana-11,13(18)-dien-28-oic acid (2), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (3), 3β,30-dihydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (4), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-3-O-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside (5), 3β,29-dihydroxy-oleana-9(11),12-dien-28-oic acid-28-O-β-d-glucopyranoside (6), namely, araliachinolic acids I and II and araliachinosides I–IV. The cytotoxicity of the isolated compounds was tested against HepG2, A549, SGC7901, and MCF7 cell lines, but no apparent activity was observed at a concentration of 50 μM. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

► Show Figures

Figure 1

15 pages, 1071 KiB

Open AccessArticle

Could a Proto-Ribosome Emerge Spontaneously in the Prebiotic World?

by Ilana C. Agmon

Molecules 2016, 21(12), 1701; https://doi.org/10.3390/molecules21121701 - 9 Dec 2016

Cited by 25 | Viewed by 6414

Abstract

An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which [...] Read more.

An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which is believed to be still embedded in the contemporary ribosome, is used to assess the feasibility of such spontaneous emergence. Three concentric structural elements of different magnitudes, having a dimeric nature derived from the symmetrical region of the ribosomal large subunit, were suggested to constitute the vestige of the proto-ribosome. It is assumed to have materialized spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and simple elongation. Probabilistic and energetic considerations are applied in order to evaluate the suitability of the three contenders for being the initial proto-ribosome. The analysis points to the simplest proto-ribosome, comprised of a dimer of tRNA-like molecules presently embedded in the core of the symmetrical region, as the only one having a realistic statistical likelihood of spontaneous emergence from random RNA chains. Hence it offers a feasible starting point for a continuous evolutionary path from the prebiotic matter, through natural processes, into the intricate modern translation system. Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

► Show Figures

Figure 1

17 pages, 3201 KiB

Open AccessArticle

Enhanced Stilbene Production and Excretion in Vitis vinifera cv Pinot Noir Hairy Root Cultures

by Leo-Paul Tisserant, Aziz Aziz, Nathalie Jullian, Philippe Jeandet, Christophe Clément, Eric Courot and Michèle Boitel-Conti

Molecules 2016, 21(12), 1703; https://doi.org/10.3390/molecules21121703 - 10 Dec 2016

Cited by 24 | Viewed by 9076

Abstract

Stilbenes are defense molecules produced by grapevine in response to stresses including various elicitors and signal molecules. Together with their prominent role in planta, stilbenes have been the center of much attention in recent decades due to their pharmaceutical properties. With the aim [...] Read more.

Stilbenes are defense molecules produced by grapevine in response to stresses including various elicitors and signal molecules. Together with their prominent role in planta, stilbenes have been the center of much attention in recent decades due to their pharmaceutical properties. With the aim of setting up a cost-effective and high purity production of resveratrol derivatives, hairy root lines were established from Vitis vinifera cv Pinot Noir 40024 to study the organ-specific production of various stilbenes. Biomass increase and stilbene production by roots were monitored during flask experiments. Although there was a constitutive production of stilbenes in roots, an induction of stilbene synthesis by methyl jasmonate (MeJA) after 18 days of growth led to further accumulation of ε-viniferin, δ-viniferin, resveratrol and piceid. The use of 100 µM MeJA after 18 days of culture in the presence of methyl-β-cyclodextrins (MCDs) improved production levels, which reached 1034µg/g fresh weight (FW) in roots and 165 mg/L in the extracellular medium, corresponding to five-and 570-foldincrease in comparison to control. Whereas a low level of stilbene excretion was measured in controls, addition of MeJA induced excretion of up to 37% of total stilbenes. The use of MCDs increased the excretion phenomenon even more, reaching up to 98%. Our results demonstrate the ability of grapevine hairy roots to produce various stilbenes. This production was significantly improved in response to elicitation by methyl jasmonate and/or MCDs. This supports the interest of using hairy roots as a potentially valuable system for producing resveratrol derivatives. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

► Show Figures

Figure 1

12 pages, 3503 KiB

Open AccessCommunication

Sugar-Annulated Oxazoline Ligands: A Novel Pd(II) Complex and Its Application in Allylic Substitution

by Jochen Kraft, Katharina Mill and Thomas Ziegler

Molecules 2016, 21(12), 1704; https://doi.org/10.3390/molecules21121704 - 10 Dec 2016

Cited by 17 | Viewed by 7036

Abstract

Two novel carbohydrate-derived pyridyl (PYOX)- and cyclopropyl (CYBOX)-substituted oxazoline ligands were prepared from d-glucosamine hydrochloride and 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose hydrochloride in two steps, respectively. The sugar-annulated PYOX ligand formed a stable metal complex with Pd(II), which was fully characterized by [...] Read more.

Two novel carbohydrate-derived pyridyl (PYOX)- and cyclopropyl (CYBOX)-substituted oxazoline ligands were prepared from d-glucosamine hydrochloride and 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose hydrochloride in two steps, respectively. The sugar-annulated PYOX ligand formed a stable metal complex with Pd(II), which was fully characterized by NMR spectroscopy and X-ray crystallography. NMR and X-ray analysis revealed a change of the conformation in the sugar moiety upon complexation with the palladium(II) species. Both glycosylated ligands resulted in high asymmetric induction (up to 98% ee) upon application as chiral ligands in the Pd-catalyzed allylic alkylation of rac-1,3-diphenylallyl acetate with dimethyl malonate (Tsuji-Trost reaction). Both ligands provided mainly the (R)-enantiomer of the alkylation product. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

► Show Figures

Graphical abstract

10 pages, 3883 KiB

Open AccessArticle

Interactions of Bovine Serum Albumin with Anti-Cancer Compounds Using a ProteOn XPR36 Array Biosensor and Molecular Docking

by Ling Zhang, Qiao-Yan Cai, Zhi-Xiong Cai, Yi Fang, Chun-Song Zheng, Li-Li Wang, Shan Lin, Da-Xin Chen and Jun Peng

Molecules 2016, 21(12), 1706; https://doi.org/10.3390/molecules21121706 - 10 Dec 2016

Cited by 18 | Viewed by 6273

Abstract

The aim of the work was to determine the interactions of a set of anti-cancer compounds with bovine serum albumin (BSA) using a ProteOn XPR36 array biosensor and molecular docking studies. The results revealed that a total of six anti-cancer compounds: gallic acid, [...] Read more.

The aim of the work was to determine the interactions of a set of anti-cancer compounds with bovine serum albumin (BSA) using a ProteOn XPR36 array biosensor and molecular docking studies. The results revealed that a total of six anti-cancer compounds: gallic acid, doxorubicin, acteoside, salvianolic acid B, echinacoside, and vincristine were able to reversibly bind to the immobilized BSA. The sensorgrams of these six compounds were globally fit to a Langmuir 1:1 interaction model for binding kinetics analysis. There were significant differences in their affinity for BSA, with doxorubicin, the weakest binding compound having 1000-fold less affinity than salvianolic acid B, the strongest binding compound. However, compounds with a similar KD often exhibited markedly different kinetics due to the differences in k_a and k_d. Molecular docking experiments demonstrated that acteoside was partially located within sub-domain IIA of BSA, whereas gallic acid bound to BSA deep within its sub-domain IIIA. In addition, the interactions between these compounds and BSA were dominated by hydrophobic forces and hydrogen bonds. Understanding the detailed information of these anti-cancer compounds can provide important insights into optimizing the interactions and activity of potential compounds during drug development. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

8 pages, 3039 KiB

Open AccessFeature PaperArticle

Expression of 3-Mercaptopyruvate Sulfurtransferase in the Mouse

by Masahiro Tomita, Noriyuki Nagahara and Takaaki Ito

Molecules 2016, 21(12), 1707; https://doi.org/10.3390/molecules21121707 - 11 Dec 2016

Cited by 41 | Viewed by 6038

Abstract

3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to [...] Read more.

3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to establish the tissue distribution of MST in mice. In the present study, the expression of MST in various organs of adult and fetal mice was analyzed by Western blotting and enzyme-immunohistochemistry. Moreover, the histology of MST gene–deficient mice was examined. Western blotting revealed that all organs examined had MST. The brain, liver, kidneys testes, and endocrine organs contained large amounts of MST, but the lungs, spleen, thymus, and small intestine did not. Immunohistochemically, the MST expression pattern varies in a cell-specific manner. In the brain, neural and glial cells are positively stained; in the lung, bronchiolar cells are preferentially stained; in the liver, hepatocytes around central veins are more strongly stained; renal convoluted cells are strongly stained; and pancreatic islets are strongly stained. Fetal tissues were studied, and MST expression was found to be similar before and after birth. Histological observation revealed no remarkable findings in MST gene–deficient mice. The present study revealed fundamental information regarding the MST expression of various organs in adult and fetal mice, and the morphological phenotype of MST gene–deficient mice. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

► Show Figures

Figure 1

15 pages, 1627 KiB

Open AccessArticle

Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways

by Wayne Young Liu, Thing-Fong Tzeng and I-Min Liu

Molecules 2016, 21(12), 1708; https://doi.org/10.3390/molecules21121708 - 11 Dec 2016

Cited by 33 | Viewed by 7111

Abstract

Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need [...] Read more.

Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

► Show Figures

Figure 1

9 pages, 2117 KiB

Open AccessArticle

Functional Analysis of the Fusarielin Biosynthetic Gene Cluster

by Aida Droce, Wagma Saei, Simon Hartung Jørgensen, Reinhard Wimmer, Henriette Giese, Rasmus Dam Wollenberg, Teis Esben Sondergaard and Jens Laurids Sørensen

Molecules 2016, 21(12), 1710; https://doi.org/10.3390/molecules21121710 - 13 Dec 2016

Cited by 18 | Viewed by 7461

Abstract

Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually [...] Read more.

Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually in a Fusarium graminearum strain overexpressing the local transcription factor. The results suggest that a trans-acting enoyl reductase (FSL5) assists the polyketide synthase FSL1 in biosynthesis of a polyketide product, which is released by hydrolysis by a trans-acting thioesterase (FSL2). Deletion of the epimerase (FSL3) resulted in accumulation of an unstable compound, which could be the released product. A novel compound, named prefusarielin, accumulated in the deletion mutant of the cytochrome P450 monooxygenase FSL4. Unlike the known fusarielins from Fusarium, this compound does not contain oxygenized decalin rings, suggesting that FSL4 is responsible for the oxygenation. Full article

(This article belongs to the Special Issue Polyketides)

► Show Figures

Figure 1

15 pages, 14364 KiB

Open AccessArticle

Plasma Processing with Fluorine Chemistry for Modification of Surfaces Wettability

by Veronica Satulu, Maria Daniela Ionita, Sorin Vizireanu, Bogdana Mitu and Gheorghe Dinescu

Molecules 2016, 21(12), 1711; https://doi.org/10.3390/molecules21121711 - 13 Dec 2016

Cited by 29 | Viewed by 7323

Abstract

Using plasma in conjunction with fluorinated compounds is widely encountered in material processing. We discuss several plasma techniques for surface fluorination: deposition of fluorocarbon thin films either by magnetron sputtering of polytetrafluoroethylene targets, or by plasma-assisted chemical vapor deposition using tetrafluoroethane as a [...] Read more.

Using plasma in conjunction with fluorinated compounds is widely encountered in material processing. We discuss several plasma techniques for surface fluorination: deposition of fluorocarbon thin films either by magnetron sputtering of polytetrafluoroethylene targets, or by plasma-assisted chemical vapor deposition using tetrafluoroethane as a precursor, and modification of carbon nanowalls by plasma treatment in a sulphur hexafluoride environment. We showed that conformal fluorinated thin films can be obtained and, according to the initial surface properties, superhydrophobic surfaces can be achieved. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

► Show Figures

Figure 1

13 pages, 722 KiB

Open AccessArticle

Long-Term Stability of New Co-Amorphous Drug Binary Systems: Study of Glass Transitions as a Function of Composition and Shelf Time

by Luz María Martínez, Marcelo Videa, Nahida González Sosa, José Héctor Ramírez and Samuel Castro

Molecules 2016, 21(12), 1712; https://doi.org/10.3390/molecules21121712 - 14 Dec 2016

Cited by 26 | Viewed by 7950

Abstract

The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order [...] Read more.

The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order to avoid crystallization, it has been a common strategy to add a second component to hinder the crystalline state and form a thermally stable co-amorphous system, that is to say, an amorphous binary system which retains its amorphous structure. The second component can be a small molecule excipient (such as a sugar or an aminoacid) or a second drug, with the advantage that a second active pharmaceutical ingredient could be used for complementary or combined therapeutic purposes. In most cases, the compositions studied are limited to 1:1, 2:1 and 1:2 molar ratios, leaving a gap of information about phase transitions and stability on the amorphous state in a wider range of compositions. In the present work, a study of novel co–amorphous formulations in which the selection of the active pharmaceutical ingredients was made according to the therapeutic effect is presented. Resistance against crystallization and behavior of glass transition temperature (

T_{g}

were studied through calorimetric measurements as a function of composition and shelf time. It was found that binary formulations with

T_{g}

temperatures higher than those of pure components presented long-term thermal stability. In addition, significant increments of

T_{g}

values, of as much as 15

^{\circ}

C, were detected as a result of glass relaxation at room temperature during storage time; this behavior of glass transition has not been previously reported for co-amorphous drugs. Based on these results, it can be concluded that monitoring behavior of

T_{g}

and relaxation processes during the first weeks of storage leads to a more objective evaluation of the thermomechanical stability of an amorphous formulation. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

► Show Figures

Figure 1

9 pages, 2661 KiB

Open AccessArticle

Hypervalent Iodine(III)-Induced Domino Oxidative Cyclization for the Synthesis of Cyclopenta[b]furans

by Mei-Huey Lin, Yu-Chun Chen, Shih-Hao Chiu, Yun-Fan Chen and Tsung-Hsun Chuang

Molecules 2016, 21(12), 1713; https://doi.org/10.3390/molecules21121713 - 21 Dec 2016

Cited by 2 | Viewed by 5343

Abstract

A new strategy for cyclopenta[b]furan synthesis mediated by hypervalent iodine(III) has been described. The approach employs diacetoxyiodobenzene-induced initial dehydrogenation to a putative trienone intermediate and triggered sequential cycloisomerization to form the cyclo-penta[b]furan targets. Full article

(This article belongs to the Special Issue Hypervalent Iodine Chemistry)

► Show Figures

Graphical abstract

14 pages, 1387 KiB

Open AccessArticle

A Novel Synthesis of Fused Uracils: Indenopyrimidopyridazines, Pyrimidopyridazines, and Pyrazolopyrimidines for Antimicrobial and Antitumor Evalution

by Samar El-Kalyoubi and Fatimah Agili

Molecules 2016, 21(12), 1714; https://doi.org/10.3390/molecules21121714 - 14 Dec 2016

Cited by 19 | Viewed by 5455

Abstract

A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial [...] Read more.

A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial and antitumor activity. Full article

► Show Figures

Figure 1

17 pages, 1715 KiB

Open AccessArticle

Synthesis, Antifungal Evaluation and In Silico Study of N-(4-Halobenzyl)amides

by Ricardo Carneiro Montes, Ana Luiza A. L. Perez, Cássio Ilan S. Medeiros, Marianna Oliveira de Araújo, Edeltrudes De Oliveira Lima, Marcus Tullius Scotti and Damião Pergentino de Sousa

Molecules 2016, 21(12), 1716; https://doi.org/10.3390/molecules21121716 - 13 Dec 2016

Cited by 14 | Viewed by 4862

Abstract

A collection of 32 structurally related N-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, ¹H- and ¹³C- [...] Read more.

A collection of 32 structurally related N-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, ¹H- and ¹³C- Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry. The compounds were then submitted to antimicrobial tests by the minimum inhibitory concentration method (MIC) and nystatin was used as a control in the antifungal assays. The purpose of the tests was to evaluate the influence of structural changes in the cinnamic and benzoic acid substructures on the inhibitory activity against strains of Candida albicans, Candida tropicalis, and Candida krusei. A quantitative structure-activity relationship (QSAR) study with KNIME v. 3.1.0 and Volsurf v. 1.0.7 softwares were realized, showing that descriptors DRDRDR, DRDRAC, L4LgS, IW4 and DD2 influence the antifungal activity of the haloamides. In general, 10 benzamides revealed fungal sensitivity, especially a vanillic amide which enjoyed the lowest MIC. The results demonstrate that a hydroxyl group in the para position, and a methoxyl at the meta position enhance antifungal activity for the amide skeletal structure. In addition, the double bond as a spacer group appears to be important for the activity of amide structures. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

10 pages, 1525 KiB

Open AccessArticle

Scoparone Inhibits LPS-Simulated Inflammatory Response by Suppressing IRF3 and ERK in BV-2 Microglial Cells

by Duk-Yeon Cho, Hyun Myung Ko, Joonsoo Kim, Byung-Wook Kim, Yo-Sep Yun, Jeong-In Park, Palanivel Ganesan, Jin-Tae Lee and Dong-Kug Choi

Molecules 2016, 21(12), 1718; https://doi.org/10.3390/molecules21121718 - 14 Dec 2016

Cited by 42 | Viewed by 9981

Abstract

Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson’s, Alzheimer’s, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial [...] Read more.

Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson’s, Alzheimer’s, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial effect of lower toxicity. Scoparone (6,7-dimethoxycoumarin), a major bioactive compound found in various plant parts, including the inner shell of chestnut (Castanea crenata), was evaluated on lipopolysaccharide (LPS)-activated BV-2 microglia cells. The results indicated that scoparone suppresses the LPS-stimulated increase of neuroinflammatory responses and inhibited the pro-inflammatory cytokine production in the BV-2 microglial cells. A mechanistic study showed that scoparone specifically inhibited the LPS-stimulated activation via a major regulation of IRF-3 and a regulation of ERK, whereby the phosphorylation in the BV-2 microglial cells is blocked. These data suggest that scoparone has anti-neuroinflammatory effects in LPS-activated BV-2 microglial cells, and could possibly be used in the development of novel drugs for the prevention and treatment of neuroinflammatory diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 1902 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

by Haibing He, Yinghua Ge, Hong Dai, Song Cui, Fei Ye, Jia Jin and Yujun Shi

Molecules 2016, 21(12), 1722; https://doi.org/10.3390/molecules21121722 - 16 Dec 2016

Cited by 11 | Viewed by 6216

Abstract

By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by ¹H-NMR, [...] Read more.

By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by ¹H-NMR, ¹³C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had good activities against PTP1B. Among them, compound 29 (IC₅₀ = 0.91 ± 0.33 μM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound 29 was identified as a competitive inhibitor of PTP1B with a K_i value of 0.78 μM in enzyme kinetic studies. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

9 pages, 1665 KiB

Open AccessArticle

Improving Free Radical Scavenging Activity of Soy Isoflavone Glycosides Daidzin and Genistin by 3′-Hydroxylation Using Recombinant Escherichia coli

by Chien-Min Chiang, Dong-Sheng Wang and Te-Sheng Chang

Molecules 2016, 21(12), 1723; https://doi.org/10.3390/molecules21121723 - 15 Dec 2016

Cited by 31 | Viewed by 6047

Abstract

The present study describes the biotransformation of a commercially available crude extract of soy isoflavones, which contained significant amounts of the soy isoflavone glycosides daidzin and genistin, by recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium. Two major products were isolated from [...] Read more.

The present study describes the biotransformation of a commercially available crude extract of soy isoflavones, which contained significant amounts of the soy isoflavone glycosides daidzin and genistin, by recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium. Two major products were isolated from the biotransformation and identified as 3′-hydroxydaidzin and 3′-hydroxygenistin, respectively, based on their mass and nuclear magnetic resonance spectral data. The two 3′-hydroxyisoflavone glycosides showed potent 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity with IC₅₀ values of 7.4 and 9.8 μM for 3′-hydroxydaidzin and 3′-hydroxygenistin, respectively. The free radical scavenging activities of the two 3′-hydroxyisoflavone glycosides were, respectively, 120 and 72 times higher than the activity of their precursors, daidzin and genistin, and were also stronger than the activity of ascorbic acid, which showed an IC₅₀ value of 15.1 μM. This is the first report of the bio-production and potential antioxidant applications of both 3′-hydroxydaidzin and 3′-hydroxygenistin. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

► Show Figures

Figure 1

15 pages, 2351 KiB

Open AccessArticle

Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development

by Agnieszka Irena Mazur-Bialy and Ewa Pocheć

Molecules 2016, 21(12), 1724; https://doi.org/10.3390/molecules21121724 - 15 Dec 2016

Cited by 46 | Viewed by 10686

Abstract

Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related [...] Read more.

Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4–1000 nM) affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7) following lipopolysaccharide stimulation (LPS; 100 ng/mL) which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1beta (IL-1β), monocyte chemotactic protein 1 (MCP-1), high-mobility group box 1 (HMGB1), transforming growth factor–beta 1 (TGFβ), interleukin 10 (IL-10), inducible nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) expression and release, macrophage migration and adipokines (adiponectin and leptin) were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1) upon culture with riboflavin supplementation (500–1000 nM), accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

► Show Figures

Figure 1

16 pages, 2413 KiB

Open AccessArticle

Half-Sandwich Ru(II) Halogenido, Valproato and 4-Phenylbutyrato Complexes Containing 2,2′-Dipyridylamine: Synthesis, Characterization, Solution Chemistry and In Vitro Cytotoxicity

by Pavel Štarha, Zdeněk Trávníček, Radka Křikavová and Zdeněk Dvořák

Molecules 2016, 21(12), 1725; https://doi.org/10.3390/molecules21121725 - 15 Dec 2016

Cited by 10 | Viewed by 6766

Abstract

Halogenido and carboxylato Ru(II) half-sandwich complexes of the general composition [Ru(η⁶-p-cym)(dpa)X]PF₆ (1–5) were prepared and thoroughly characterized with various techniques (e.g., mass spectrometry, NMR spectroscopy and X-ray analysis); dpa = 2,2′-dipyridylamine; p-cym = [...] Read more.

Halogenido and carboxylato Ru(II) half-sandwich complexes of the general composition [Ru(η⁶-p-cym)(dpa)X]PF₆ (1–5) were prepared and thoroughly characterized with various techniques (e.g., mass spectrometry, NMR spectroscopy and X-ray analysis); dpa = 2,2′-dipyridylamine; p-cym = p-cymene; X = Cl⁻ (for 1), Br⁻ (for 2), I⁻ (for 3), valproate(1−) (for 4) or 4-phenylbutyrate(1−) (for 5). A single-crystal X-ray analysis showed a pseudo-octahedral piano-stool geometry of [Ru(η⁶-p-cym)(dpa)I]PF₆ (3), with a η⁶-coordinated p-cymene, bidentate N-donor dpa ligand and iodido ligand coordinated to the Ru(II) atom. The results of the ¹H-NMR solution behaviour studies proved that the complexes 1–5 hydrolyse were in the mixture of solvents used (10% MeOD-d₄/90% D₂O). Complexes 1–5 were in vitro inactive against the A2780 human ovarian carcinoma cell line, up to the highest tested concentration (IC₅₀ > 100 μM). Full article

(This article belongs to the Section Organometallic Chemistry)

► Show Figures

Figure 1

15 pages, 4330 KiB

Open AccessArticle

Phase and Index of Refraction Imaging by Hyperspectral Reflectance Confocal Microscopy

by Stefano Selci

Molecules 2016, 21(12), 1727; https://doi.org/10.3390/molecules21121727 - 16 Dec 2016

Cited by 7 | Viewed by 8468

Abstract

A hyperspectral reflectance confocal microscope (HSCM) was realized by CNR-ISC (Consiglio Nazionale delle Ricerche-Istituto dei Sistemi Complessi) a few years ago. The instrument and data have been already presented and discussed. The main activity of this HSCM has been within biology, and reflectance [...] Read more.

A hyperspectral reflectance confocal microscope (HSCM) was realized by CNR-ISC (Consiglio Nazionale delle Ricerche-Istituto dei Sistemi Complessi) a few years ago. The instrument and data have been already presented and discussed. The main activity of this HSCM has been within biology, and reflectance data have shown good matching between spectral signatures and the nature or evolution on many types of cells. Such a relationship has been demonstrated mainly with statistical tools like Principal Component Analysis (PCA), or similar concepts, which represent a very common approach for hyperspectral imaging. However, the point is that reflectance data contains much more useful information and, moreover, there is an obvious interest to go from reflectance, bound to the single experiment, to reflectivity, or other physical quantities, related to the sample alone. To accomplish this aim, we can follow well-established analyses and methods used in reflectance spectroscopy. Therefore, we show methods of calculations for index of refraction n, extinction coefficient k and local thicknesses of frequency starting from phase images by fast Kramers-Kronig (KK) algorithms and the Abeles matrix formalism. Details, limitations and problems of the presented calculations as well as alternative procedures are given for an example of HSCM images of red blood cells (RBC). Full article

(This article belongs to the Special Issue Vibrational Spectroscopic Imaging and Mapping)

► Show Figures

Figure 1

14 pages, 1543 KiB

Open AccessArticle

Simultaneous Qualitation and Quantitation of Chlorogenic Acids in Kuding Tea Using Ultra-High-Performance Liquid Chromatography–Diode Array Detection Coupled with Linear Ion Trap–Orbitrap Mass Spectrometer

by Yanyun Che, Zhibin Wang, Zhiyun Zhu, Yangyang Ma, Yaqiong Zhang, Wen Gu, Jiayu Zhang and Gaoxiong Rao

Molecules 2016, 21(12), 1728; https://doi.org/10.3390/molecules21121728 - 16 Dec 2016

Cited by 25 | Viewed by 5125

Abstract

Kuding tea, the leaves of Ilex Kudingcha C.J. Tseng, has been applied for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and so on. The chlorogenic acids (CGAs) in Kuding tea have shown excellent antioxidative, antiobesity, anti-atherosclerotic and anticancer activities. Nevertheless, the chemical profiles of [...] Read more.

Kuding tea, the leaves of Ilex Kudingcha C.J. Tseng, has been applied for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and so on. The chlorogenic acids (CGAs) in Kuding tea have shown excellent antioxidative, antiobesity, anti-atherosclerotic and anticancer activities. Nevertheless, the chemical profiles of CGAs in Kuding tea have not been comprehensively studied yet, which hinders further quality control. In the present study, a sensitive ultra-high-performance liquid chromatography-diode array detection coupled with a linear ion trap-Orbitrap (UHPLC-DAD-LTQ-Orbitrap) method was established to screen and identify CGAs in Kuding tea. Six CGA standards were first analyzed in negative ion mode with a CID-MS/MS experiment and then the diagnostic product ions (DPIs) were summarized. According to the retention behavior in the RP-ODS column, accurate mass measurement, DPIs and relevant bibliography data, a total of 68 CGA candidates attributed to 12 categories were unambiguously or preliminarily screened and characterized within 18 min of chromatographic time. This was the first systematic report on the distribution of CGAs in Kuding tea. Meanwhile, the contents of 6 major CGAs in Kuding tea were also determined by the UHPLC-DAD method. All the results indicated that the established analytical method could be employed as an effective technique for the comprehensive and systematic characterization of CGAs and quality control of the botanic extracts or Chinese medicinal formulas that contain various CGAs. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 1473 KiB

Open AccessArticle

Chemical Studies of Yellow Tamarillo (Solanum betaceum Cav.) Fruit Flavor by Using a Molecular Sensory Approach

by Juliana María García, Laura Juliana Prieto, Alirio Guevara, Diana Malagon and Coralia Osorio

Molecules 2016, 21(12), 1729; https://doi.org/10.3390/molecules21121729 - 16 Dec 2016

Cited by 31 | Viewed by 10132

Abstract

The odor-active volatile compounds of yellow tamarillo fruit (S. betaceum Cav.) were identified and quantified by using a sensomics approach, combining a gentle volatile extraction (solvent-assisted flavor evaporation (SAFE)), gas chromatography-mass spectrometry (GC-MS), and sensory analyses (gas chromatography-olfactometry (GC-O) and aroma extract [...] Read more.

The odor-active volatile compounds of yellow tamarillo fruit (S. betaceum Cav.) were identified and quantified by using a sensomics approach, combining a gentle volatile extraction (solvent-assisted flavor evaporation (SAFE)), gas chromatography-mass spectrometry (GC-MS), and sensory analyses (gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA)). The medium-term purpose of this work is to evaluate the change of odor-active volatiles during processing. Thus, (Z)-3-hexenal, hexanal, and ethyl butanoate were identified as key aroma compounds of yellow tamarillo. The C₆-aliphatic compounds, aliphatic esters, and terpenols were characterized as the volatiles responsible for the herbal-green, fruity, and fresh-mint odor notes of this variety, respectively. Additionally, one non-volatile compound contributing to the residual bitter taste of this fruit was isolated by a bioguided (taste sensory analyses) fractionation. The freeze-dried fruit was sequentially liquid-liquid partitioned with solvents of different polarity, and then the ethyl acetate fraction was submitted to size exclusion chromatography. Then, its structure was elucidated as rosmarinic acid, by using common spectroscopic methods (mass spectrometry (MS) and nuclear magnetic resonance (NMR)). The amount of rosmarinic acid was quantified as 46.17 ± 1.20 mg/100 g of dried fruit, by the external standard method. Its bitter taste threshold value was determined by using the 3AFC (alternative forced choice) method to be 37.00 ± 1.25 mg/L. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

► Show Figures

Figure 1

18 pages, 1452 KiB

Open AccessArticle

Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver

by Fan Peng, Xin Guo, Zhihong Li, Changzheng Li, Changdong Wang, Weiran Lv, Junjie Wang, Fangxiang Xiao, Mohammad Amjad Kamal and Chengfu Yuan

Molecules 2016, 21(12), 1731; https://doi.org/10.3390/molecules21121731 - 16 Dec 2016

Cited by 31 | Viewed by 5963

Abstract

Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune [...] Read more.

Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enriched P. fortuneana (Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

► Show Figures

Figure 1

12 pages, 1777 KiB

Open AccessArticle

Simultaneous Determination of Multiple Components in Guanjiekang in Rat Plasma via the UPLC–MS/MS Method and Its Application in Pharmacokinetic Study

by Jian Wu, Ying Xie, Zheng Xiang, Canjian Wang, Hua Zhou and Liang Liu

Molecules 2016, 21(12), 1732; https://doi.org/10.3390/molecules21121732 - 16 Dec 2016

Cited by 18 | Viewed by 6311

Abstract

Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of [...] Read more.

Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of active components in GJK remains unclear. This study aims to evaluate the pharmacokinetic behavior of seven representative active constituents in GJK (i.e., benzoylhypaconine, benzoylmesaconine, paeoniflorin, tetrahydropalmatine, calycosin-7-glucoside, formononetin and isoliquiritigenin) after oral administration of GJK in rats. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometer (UPLC–MS/MS) method has been successfully developed for the simultaneous determination of these seven constituents in rat plasma. Chromatographic separation was achieved on a C₁₈ column with a gradient elution program that consists of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.35 mL/min. Detection was performed under the multiple reaction monitoring (MRM) in the positive electrospray ionization (ESI) mode. The calibration curves exhibited good linearity (R² > 0.99) over a wide concentration range for all constituents. The accuracies ranged from 92.9% to 107.8%, and the intra-day and inter-day precisions at three different levels were below 15%. Our PK results showed that these seven compounds were quickly absorbed after the administration of the GJK product, and T_max ranged from 30 min to 189 min. The in vivo concentrations of paeoniflorin and isoliquiritigenin were significantly higher than the reported in vitro effective doses, indicating that they could partly contribute to the therapeutic effect of GJK. Therefore, we conclude that pharmacokinetic studies of representative bioactive chemicals after administration of complex herbal products are not only necessary but also feasible. Moreover, these seven compounds that were absorbed in vivo can be used as indicator standards for quality control and for determining pharmacokinetic behavior of herbal medicines in clinical studies. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Figure 1

11 pages, 1398 KiB

Open AccessArticle

Validation and Application of an Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Yuanhuacine Determination in Rat Plasma after Pulmonary Administration: Pharmacokinetic Evaluation of a New Drug Delivery System

by Man Li, Xiao Liu, Hao Cai, Zhichun Shen, Liu Xu, Weidong Li, Li Wu, Jinao Duan and Zhipeng Chen

Molecules 2016, 21(12), 1733; https://doi.org/10.3390/molecules21121733 - 16 Dec 2016

Cited by 5 | Viewed by 4699

Abstract

Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to [...] Read more.

Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to alleviate the adverse toxicity effects, we tried to deliver yuanhuacine directly into the lungs. Ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) was used to detect the analyte and IS. After extraction (ether:dichloromethane = 8:1), the analyte and IS were separated on a Waters BEH-C₁₈ column (100 mm × 2.1 mm, 1.7 μm) under a 5 min gradient elution using a mixture of acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL/min. ESI positive mode was chosen for detection. The method was fully validated for its selectivity, accuracy, precision, stability, matrix effect, and extraction recovery. This new method for yuanhuacine concentration determination in rat plasma was reliable and could be applied for its preclinical and clinical monitoring purpose. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

12 pages, 1067 KiB

Open AccessArticle

Volatile and Nonvolatile Constituents and Antioxidant Capacity of Oleoresins in Three Taiwan Citrus Varieties as Determined by Supercritical Fluid Extraction

by Min-Hung Chen and Tzou-Chi Huang

Molecules 2016, 21(12), 1735; https://doi.org/10.3390/molecules21121735 - 17 Dec 2016

Cited by 34 | Viewed by 7018

Abstract

As local varieties of citrus fruit in Taiwan, Ponkan (Citrus reticulata Blanco), Tankan (C. tankan Hayata), and Murcott (C. reticulate × C. sinensis) face substantial competition on the market. In this study, we used carbon dioxide supercritical technology to [...] Read more.

As local varieties of citrus fruit in Taiwan, Ponkan (Citrus reticulata Blanco), Tankan (C. tankan Hayata), and Murcott (C. reticulate × C. sinensis) face substantial competition on the market. In this study, we used carbon dioxide supercritical technology to extract oleoresin from the peels of the three citrus varieties, adding alcohol as a solvent assistant to enhance the extraction rate. The supercritical fluid extraction was fractionated with lower terpene compounds in order to improve the oxygenated amounts of the volatile resins. The contents of oleoresin from the three varieties of citrus peels were then analyzed with GC/MS in order to identify 33 volatile compounds. In addition, the analysis results indicated that the non-volatile oleoresin extracted from the samples contains polymethoxyflavones (86.2~259.5 mg/g), limonoids (111.7~406.2 mg/g), and phytosterols (686.1~1316.4 μg/g). The DPPH (1,1-Diphenyl-2-picrylhydrazyl), ABTS [2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] scavenging and inhibition of lipid oxidation, which test the oleoresin from the three kinds of citrus, exhibited significant antioxidant capacity. The component polymethoxyflavones contributed the greatest share of the overall antioxidant capacity, while the limonoid and phytosterol components effectively coordinated with its effects. Full article

► Show Figures

Figure 1

19 pages, 3139 KiB

Open AccessArticle

Synthesis and Structural Investigation of New Bio-Relevant Complexes of Lanthanides with 5-Hydroxyflavone: DNA Binding and Protein Interaction Studies

by Alexandra-Cristina Munteanu, Mihaela Badea, Rodica Olar, Luigi Silvestro, Constanţa Dulea, Constantin-Daniel Negut and Valentina Uivarosi

Molecules 2016, 21(12), 1737; https://doi.org/10.3390/molecules21121737 - 16 Dec 2016

Cited by 21 | Viewed by 7044

Abstract

In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III), Eu(III), Gd(III), Tb(III). The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral [...] Read more.

In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III), Eu(III), Gd(III), Tb(III). The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral studies. The general chemical formula of the complexes is [Ln(C₁₅H₉O₃)₃(OH)₂(H₂O)_x]·nH₂O, where Ln is the lanthanide cation and x = 0 for Sm(III), x = 1 for Eu(III), Gd(III), Tb(III) and n = 0 for Sm(III), Gd(III), Tb(III), n = 1 for Eu(III), respectively. The proposed structures of the complexes were optimized by DFT calculations. Theoretical calculations and experimental determinations sustain the proposed structures of the hydroxo complexes, with two molecules of 5-hydroxyflavone acting as monoanionic bidentate chelate ligands. The interaction of the complexes with calf thymus DNA has been explored by fluorescence titration and UV-Vis absorption binding studies, and revealed that the synthesized complexes interact with DNA with binding constants (K_b) ~ 10⁴. Human serum albumin (HSA) and transferrin (Tf) binding studies have also been performed by fluorescence titration techniques (fluorescence quenching studies, synchronous fluorescence spectra). The apparent association constants (K_a) and thermodynamic parameters have been calculated from the fluorescence quenching experiment at 299 K, 308 K, and 318 K. The quenching curves indicate that the complexes bind to HSA with smaller affinity than the ligand, but to Tf with higher binding affinities than the ligand. Full article

(This article belongs to the Section Organometallic Chemistry)

► Show Figures

Graphical abstract

8 pages, 907 KiB

Open AccessArticle

Safe Synthesis of Alkylhydroxy and Alkylamino Nitramines

by Simen Antonsen, Marius Aursnes, Harrison Gallantree-Smith, Christian Dye and Yngve Stenstrøm

Molecules 2016, 21(12), 1738; https://doi.org/10.3390/molecules21121738 - 16 Dec 2016

Cited by 8 | Viewed by 6437

Abstract

Three different protocols for the syntheses of hydroxyalkylnitramines are presented and compared. Safety issues regarding the synthesis of nitramines are also discussed. Full article

(This article belongs to the Section Green Chemistry)

► Show Figures

Graphical abstract

11 pages, 1331 KiB

Open AccessArticle

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion

by Virginia Chamorro, Rachele Pandolfi, Laura Moreno, Bianca Barreira, Andrea Martínez-Ramas, Daniel Morales-Cano, Jesús Ruiz-Cabello, José Angel Lorente, Juan Duarte, Ángel Cogolludo, José Luis Alvarez-Sala and Francisco Perez-Vizcaino

Molecules 2016, 21(12), 1739; https://doi.org/10.3390/molecules21121739 - 20 Dec 2016

Cited by 13 | Viewed by 6058

Abstract

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min [...] Read more.

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. Results: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan–Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. Conclusions: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

► Show Figures

Figure 1

12 pages, 2866 KiB

Open AccessArticle

Photochemically Immobilized 4-Methylbenzoyl Cellulose as a Powerful Chiral Stationary Phase for Enantioselective Chromatography

by Eric Francotte, Dan Huynh and Tong Zhang

Molecules 2016, 21(12), 1740; https://doi.org/10.3390/molecules21121740 - 17 Dec 2016

Cited by 15 | Viewed by 5226

Abstract

A process to immobilize para-methylbenzoyl cellulose (PMBC) on silica gel has been developed and applied to prepare chiral stationary phases (CSPs) for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a [...] Read more.

A process to immobilize para-methylbenzoyl cellulose (PMBC) on silica gel has been developed and applied to prepare chiral stationary phases (CSPs) for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a silica gel support. The influence of parameters such as irradiation time and solvent on immobilization effectiveness were investigated. The performance of the prepared immobilized phases were evaluated by injection of a series of racemic compounds onto the packed columns and determination of their chiral recognition ability. By contrast to the classical coated phase, the immobilized CSP can be used under various chromatographic conditions without limitation of organic solvent types as the mobile phase. This extended applicability permits to improve selectivity and to resolve chiral compounds which are not or only poorly soluble in the mobile phases which are compatible with the non-immobilized PMBC stationary phase. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

► Show Figures

Figure 1

17 pages, 1974 KiB

Open AccessArticle

DeBouganin Diabody Fusion Protein Overcomes Drug Resistance to ADCs Comprised of Anti-Microtubule Agents

by Shilpa Chooniedass, Rachelle L. Dillon, Arjune Premsukh, Peter J. Hudson, Gregory P. Adams, Glen C. MacDonald and Jeannick Cizeau

Molecules 2016, 21(12), 1741; https://doi.org/10.3390/molecules21121741 - 17 Dec 2016

Cited by 6 | Viewed by 5952

Abstract

Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. [...] Read more.

Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. However, ADC potency can be altered by mechanisms of resistance such as overexpression of efflux pumps or anti-apoptotic proteins. DeBouganin is a de-immunized variant of bouganin, a ribosome-inactivating protein (RIP) that blocks protein synthesis, thereby leading to apoptosis. When conjugated to trastuzumab (T-deB), deBouganin was more potent than ado-trastuzumab-emtansine (T-DM1) and unaffected by resistance mechanisms to which DM1 is susceptible. To further highlight the differentiating mechanism of action of deBouganin, HCC1419 and BT-474 tumor cells that survived T-DM1 or trastuzumab-MMAE (T-MMAE) treatment were treated with an anti-HER2 C6.5 diabody–deBouganin fusion protein or T-deB. C6.5 diabody–deBouganin and T-deB were potent against HCC1419 and BT-474 cells that were resistant to T-DM1 or T-MMAE killing. The resistant phenotype involved MDR pumps, Bcl-2 family members, and the presence of additional unknown pathways. Overall, the data suggest that deBouganin is effective against tumor cell resistance mechanisms selected in response to ADCs composed of anti-microtubule payloads. Full article

(This article belongs to the Special Issue Ribosome-Inactivating Proteins--Commemorative Issue in Honor of Professor Fiorenzo Stirpe)

► Show Figures

Figure 1

14 pages, 2435 KiB

Open AccessArticle

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes

by Ladislav Habala, Samuel Varényi, Andrea Bilková, Peter Herich, Jindra Valentová, Jozef Kožíšek and Ferdinand Devínsky

Molecules 2016, 21(12), 1742; https://doi.org/10.3390/molecules21121742 - 17 Dec 2016

Cited by 31 | Viewed by 8322

Abstract

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. [...] Read more.

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

► Show Figures

Graphical abstract

14 pages, 3639 KiB

Open AccessArticle

Chemical Basis of the Fungicidal Activity of Tobacco Extracts against Valsa mali

by Chemical Basis of the Fungicidal Activity of Tobacco Extracts against Valsa mali Suzhen Duan, Yongmei Du, Xiaodong Hou, Ning Yan, Weijie Dong, Xinxin Mao and Zhongfeng Zhang

Molecules 2016, 21(12), 1743; https://doi.org/10.3390/molecules21121743 - 18 Dec 2016

Cited by 38 | Viewed by 6493

Abstract

Under pressure from social criticism and an unclear future, tobacco researchers have begun to seek alternative uses for the product. Here, we present our study on isolating tobacco compounds with fungicidal activity, which could be used as plant-derived pesticides. Using
Valsa mali as [...] Read more.

Under pressure from social criticism and an unclear future, tobacco researchers have begun to seek alternative uses for the product. Here, we present our study on isolating tobacco compounds with fungicidal activity, which could be used as plant-derived pesticides. Using
Valsa mali as the target fungus, agar plate tests were conducted to evaluate the fungicidal activity of various tobacco extracts, including tobacco leaves extracts prepared with different solvents, extracts of different tobacco cultivars, and samples from different tobacco organs. Fungal growth morphology was used as the criterion to evaluate the fungicidal activity of tobacco extracts. Correlation analyses between the fungicidal activities and the chemical components of tobacco extracts indicated the major chemical constituents with fungicidal activity. Then, the active compounds were isolated and their effects on the ultra-microstructures of V. mali was analyzed using scanning- and transmission-electron microscopy. The results suggested that tobacco extracts prepared with solvents of weaker polarity had higher fungicidal activity, and the inhibitory activity of tobacco extracts against V. mali was also cultivar dependent. Furthermore, the fungicidal effects of tobacco flower extracts were higher than those of the leaf extracts. Chemical analysis indicated that cembranoids were the main fungicidal substances, which act by destroying the endometrial structure of the fungus. Tobacco cembranoids at 80 μg/mL could completely inhibit the growth of V. mali, with an EC₅₀ value of 13.18 μg/mL. Our study therefore suggests that tobacco leaves and inflorescences are excellent plant resources for the biological control of V. mali. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

► Show Figures

Figure 1

17 pages, 1929 KiB

Open AccessArticle

Combined Use of S. pombe and L. thermotolerans in Winemaking. Beneficial Effects Determined Through the Study of Wines’ Analytical Characteristics

by Ángel Benito, Fernando Calderón and Santiago Benito

Molecules 2016, 21(12), 1744; https://doi.org/10.3390/molecules21121744 - 18 Dec 2016

Cited by 58 | Viewed by 6961

Abstract

The most common way to produce red wine is through the use of Saccharomyces cerevisiae strains for alcoholic fermentation and lactic acid bacteria for malolactic fermentation. This traditional winemaking methodology produces microbiologically stable red wines. However, under specific conditions off-flavours can occur, wine [...] Read more.

The most common way to produce red wine is through the use of Saccharomyces cerevisiae strains for alcoholic fermentation and lactic acid bacteria for malolactic fermentation. This traditional winemaking methodology produces microbiologically stable red wines. However, under specific conditions off-flavours can occur, wine quality can suffer and human health problems are possible, especially after the second fermentation by the lactic acid bacteria. In warm countries, problems during the malolactic fermentation arise because of the high pH of the must, which makes it very difficult to properly control the process. Under such conditions, wines with high acetic acid and histamine concentrations are commonly produced. This study investigates a recent red
wine-making technology that uses a combination of Lachancea thermotolerans and Schizosaccharomyces pombe as an alternative to the conventional malolactic fermentation. This work studies new parameters such as aroma compounds, amino acids, ethanol index and sensory evaluation. Schizosaccharomyces pombe totally consumes malic acid while Lachancea thermotolerans produces lactic acid, avoiding excessive deacidification of musts with low acidity in warm viticulture areas. This methodology also reduces the malolactic fermentation hazards in wines with low acidity. The main products are wines that contain less acetic acid, less biogenic amines and precursors and less ethyl carbamate precursors than the traditional wines produced via conventional fermentation techniques. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

10 pages, 906 KiB

Open AccessArticle

Characterization of Fractional Polysaccharides from Gleditsia sinensis and Gleditsia microphylla Gums

by Yantao Liu, Zhenglong Xu, Weian Zhang, Jiufang Duan, Jianxin Jiang and Dafeng Sun

Molecules 2016, 21(12), 1745; https://doi.org/10.3390/molecules21121745 - 19 Dec 2016

Cited by 23 | Viewed by 5945

Abstract

The seeds of Gleditsia sinensis and Gleditsia microphylla, widespread in China, are an important source of galactomannans. G. sinensis gum (GSG) and G. microphylla gum (GMG) were purified and precipitated using different concentrations of ethanol and isopropanol. The GSG and GMG, precipitated [...] Read more.

The seeds of Gleditsia sinensis and Gleditsia microphylla, widespread in China, are an important source of galactomannans. G. sinensis gum (GSG) and G. microphylla gum (GMG) were purified and precipitated using different concentrations of ethanol and isopropanol. The GSG and GMG, precipitated in different stages, presented different characteristics, including polymer recovery, mannose/galactose ratio, chemical composition, molecular weight, and morphological appearance. The galactomannan recovery of GSG and GMG in 33.3% ethanol was 81.7% and 82.5%, respectively, while that in 28.8% isopropanol was 81.3% and 82.9%, respectively. To achieve similar precipitation efficiency, the amount of isopropanol should be lower than that of ethanol because of the lower dielectric constant of isopropanol (20 vs. 25 for ethanol). The precipitation behavior of galactomannans in polar organic solvents was dependent on the molecular structures and properties of the solvent. A higher mannose/galactose ratio and a higher molecular weight was obtained in a lower concentration of alcohols. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

► Show Figures

Figure 1

10 pages, 2721 KiB

Open AccessArticle

Targeting Cancer Stem Cells with Novel 4-(4-Substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thiones

by Mashooq Ahmad Bhat, Abdullah Al-Dhfyan and Mohamed A. Al-Omar

Molecules 2016, 21(12), 1746; https://doi.org/10.3390/molecules21121746 - 19 Dec 2016

Cited by 26 | Viewed by 6304

Abstract

Novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thione derivatives (DHP 1–9) were designed, synthesized, characterized and evaluated for antitumor activity against cancer stem cells. The compounds were synthesized in one pot. Enaminones E1 and E2 were reacted with substituted benzaldehydes and urea/thiourea [...] Read more.

Novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thione derivatives (DHP 1–9) were designed, synthesized, characterized and evaluated for antitumor activity against cancer stem cells. The compounds were synthesized in one pot. Enaminones E1 and E2 were reacted with substituted benzaldehydes and urea/thiourea in the presence of glacial acetic acid. The synthesized compounds were characterized by spectral analysis. The compounds were screened in vitro against colon cancer cell line (LOVO) colon cancer stem cells. Most of the compounds were found to be active against side population cancer stem cells with an inhibition of >50% at a 10 μM concentration. Compounds DHP-1, DHP-7 and DHP-9 were found to be inactive. Compound DHP-5 exhibited an in vitro anti-proliferative effect and arrested cancer cells at the Gap 2 phase (G2) checkpoint and demonstrated an inhibitory effect on tumor growth for a LOVO xenograft in a nude mouse experiment. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Graphical abstract

12 pages, 1331 KiB

Open AccessArticle

New Iridoid Glucosides from Caryopteris incana (Thunb.) Miq. and Their α-Glucosidase Inhibitory Activities

by Xu-Dong Mao, Gui-Xin Chou, Sen-Miao Zhao and Cheng-Gang Zhang

Molecules 2016, 21(12), 1749; https://doi.org/10.3390/molecules21121749 - 21 Dec 2016

Cited by 11 | Viewed by 5479

Abstract

In our continued investigations of the plant Caryopteris incana, five new iridoid glucosides 1–5, including two cis-trans-isomers, 3 and 4, along with six known compounds 6–11, were isolated from the n-butyl alcohol ( [...] Read more.

In our continued investigations of the plant Caryopteris incana, five new iridoid glucosides 1–5, including two cis-trans-isomers, 3 and 4, along with six known compounds 6–11, were isolated from the n-butyl alcohol (n-BuOH) soluble fraction of whole dried material of Caryopteris incana. Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, all isolates were evaluated for their yeast α-glucosidase inhibitory effects. Among these compounds, 4–8 and 10 exhibited potent inhibition of α-glucosidase. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

11 pages, 562 KiB

Open AccessArticle

Comparative Study on the Characteristics of Weissella cibaria CMU and Probiotic Strains for Oral Care

by Hye-Jin Jang, Mi-Sun Kang, Sung-Hun Yi, Ji-Young Hong and Sang-Pil Hong

Molecules 2016, 21(12), 1752; https://doi.org/10.3390/molecules21121752 - 20 Dec 2016

Cited by 56 | Viewed by 8702

Abstract

Probiotics have been demonstrated as a new paradigm to substitute antibiotic treatment for dental caries, gingivitis, and chronic periodontitis. The present work was conducted to compare the characteristics of oral care probiotics: Weissella cibaria CMU (Chonnam Medical University) and four commercial probiotic strains. [...] Read more.

Probiotics have been demonstrated as a new paradigm to substitute antibiotic treatment for dental caries, gingivitis, and chronic periodontitis. The present work was conducted to compare the characteristics of oral care probiotics: Weissella cibaria CMU (Chonnam Medical University) and four commercial probiotic strains. Survival rates under poor oral conditions, acid production, hydrogen peroxide production, as well as inhibition of biofilm formation, coaggregation, antibacterial activity, and inhibition of volatile sulfur compounds were evaluated. The viability of W. cibaria CMU was not affected by treatment of 100 mg/L lysozyme for 90 min and 1 mM hydrogen peroxide for 6 h. Interestingly, W. cibaria produced less acid and more hydrogen peroxide than the other four probiotics. W. cibaria inhibited biofilm formation by Streptococcus mutans at lower concentrations (S. mutans/CMU = 8) and efficiently coaggregated with Fusobacterium nucleatum. W. cibaria CMU and two commercial probiotics, including Lactobacillus salivarius and Lactobacillus reuteri, showed high antibacterial activities (>97%) against cariogens (S. mutans and Streptococcus sobrinus), and against periodontopathogens (F. nucleatum and Porphyromonas gingivalis). All of the lactic acid bacterial strains in this study significantly reduced levels of hydrogen sulfide and methyl mercaptan produced by F. nucleatum and P. gingivalis (p < 0.05). These results suggest that W. cibaria CMU is applicable as an oral care probiotic. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

► Show Figures

Figure 1

10 pages, 1648 KiB

Open AccessArticle

Chemical Fingerprint Analysis and Quantitative Analysis of Rosa rugosa by UPLC-DAD

by Sanawar Mansur, Rahima Abdulla, Amatjan Ayupbec and Haji Akbar Aisa

Molecules 2016, 21(12), 1754; https://doi.org/10.3390/molecules21121754 - 21 Dec 2016

Cited by 13 | Viewed by 6933

Abstract

A method based on ultra performance liquid chromatography with a diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of R. rugosa collected from different plantations in the Xinjiang [...] Read more.

A method based on ultra performance liquid chromatography with a diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of R. rugosa collected from different plantations in the Xinjiang region of China were used to establish the fingerprint. The feasibility and advantages of the used UPLC fingerprint were verified for its similarity evaluation by systematically comparing chromatograms with professional analytical software recommended by State Food and Drug Administration (SFDA) of China. In quantitative analysis, the five compounds showed good regression (R² = 0.9995) within the test ranges, and the recovery of the method was in the range of 94.2%–103.8%. The similarities of liquid chromatography fingerprints of 10 batches of R. rugosa were more than 0.981. The developed UPLC fingerprint method is simple, reliable, and validated for the quality control and identification of R. rugosa. Additionally, simultaneous quantification of five major bioactive ingredients in the R. rugosa samples was conducted to interpret the consistency of the quality test. The results indicated that the UPLC fingerprint, as a characteristic distinguishing method combining similarity evaluation and quantification analysis, can be successfully used to assess the quality and to identify the authenticity of R. rugosa. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

16 pages, 1013 KiB

Open AccessArticle

Polyphenol Composition, Antioxidant Activity and Cytotoxicity of Seeds from Two Underexploited Wild Licania Species: L. rigida and L. tomentosa

by Igor Parra Pessoa, José Joaquim Lopes Neto, Thiago Silva de Almeida, Davi Felipe Farias, Leonardo Rogério Vieira, Jackeline Lima de Medeiros, Aline Augusti Boligon, Ad Peijnenburg, Ivan Castelar and Ana Fontenele Urano Carvalho

Molecules 2016, 21(12), 1755; https://doi.org/10.3390/molecules21121755 - 21 Dec 2016

Cited by 16 | Viewed by 7308

Abstract

Studies have shown the benefit of antioxidants in the prevention or treatment of human diseases and promoted a growing interest in new sources of plant antioxidants for pharmacological use. This study aimed to add value to two underexploited wild plant species (Licania [...] Read more.

Studies have shown the benefit of antioxidants in the prevention or treatment of human diseases and promoted a growing interest in new sources of plant antioxidants for pharmacological use. This study aimed to add value to two underexploited wild plant species (Licania rigida) and L. tomentosa) from Brazilian flora. Thus, the phenolic compounds profile of their seed ethanol extract and derived fractions were elucidated by HPLC, the antioxidant capacity was assessed by in vitro chemical tests and the cytotoxicity determined using the human carcinoma cell lines MCF-7 and Caco-2. Eleven phenolic compounds were identified in the extracts of each species. The extracts and fractions showed excellent antioxidant activity in the DPPH assay (SC₅₀, ranging from 9.15 to 248.8 µg/mL). The aqueous fraction of L. rigida seeds was most effective in preventing lipid peroxidation under basal conditions (IC₅₀ 60.80 µg/mL) whereas, in the presence of stress inducer, the methanolic fraction of L. tomentosa performed best (IC₅₀ 8.55 µg/mL). None of the samples showed iron chelating capacity. Ethanolic seed extracts of both species did not reveal any cytotoxicity against MCF-7 and Caco-2 cells. Both plant species showed a promising phenolic profile with potent antioxidant capacity and deserve attention to be sustainably explored. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

15 pages, 7885 KiB

Open AccessArticle

Inhibition of Hypoxia-Induced Retinal Angiogenesis by Specnuezhenide, an Effective Constituent of Ligustrum lucidum Ait., through Suppression of the HIF-1α/VEGF Signaling Pathway

by Jianming Wu, Xiao Ke, Wei Fu, Xiaoping Gao, Hongcheng Zhang, Wei Wang, Na Ma, Manxi Zhao, Xiaofeng Hao and Zhirong Zhang

Molecules 2016, 21(12), 1756; https://doi.org/10.3390/molecules21121756 - 21 Dec 2016

Cited by 49 | Viewed by 8058

Abstract

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion [...] Read more.

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 μM CoCl₂ to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1, 1.0 μg/mL) or SPN (0.2, 1.0 and 5.0 μg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

► Show Figures

Figure 1

14 pages, 1500 KiB

Open AccessArticle

Pharmacological Properties of Riparin IV in Models of Pain and Inflammation

by Olívia Azevêdo Nascimento, Renan Fernandes do Espírito-Santo, Luíza Carolina França Opretzka, José Maria Barbosa-Filho, Stanley Juan Chavez Gutierrez, Cristiane Flora Villarreal and Milena Botelho Pereira Soares

Molecules 2016, 21(12), 1757; https://doi.org/10.3390/molecules21121757 - 21 Dec 2016

Cited by 24 | Viewed by 5854

Abstract

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory [...] Read more.

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56–100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED₅₀ values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56–25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund’s adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

► Show Figures

Graphical abstract

18 pages, 5641 KiB

Open AccessArticle

Cryptolepine, a Plant Alkaloid, Inhibits the Growth of Non-Melanoma Skin Cancer Cells through Inhibition of Topoisomerase and Induction of DNA Damage

by Harish C. Pal and Santosh K. Katiyar

Molecules 2016, 21(12), 1758; https://doi.org/10.3390/molecules21121758 - 21 Dec 2016

Cited by 49 | Viewed by 7656

Abstract

Topoisomerases have been shown to have roles in cancer progression. Here, we have examined the effect of cryptolepine, a plant alkaloid, on the growth of human non-melanoma skin cancer cells (NMSCC) and underlying mechanism of action. For this purpose SCC-13 and A431 cell [...] Read more.

Topoisomerases have been shown to have roles in cancer progression. Here, we have examined the effect of cryptolepine, a plant alkaloid, on the growth of human non-melanoma skin cancer cells (NMSCC) and underlying mechanism of action. For this purpose SCC-13 and A431 cell lines were used as an in vitro model. Our study reveals that SCC-13 and A431 cells express higher levels as well as activity of topoisomerase (Topo I and Topo II) compared with normal human epidermal keratinocytes. Treatment of NMSCC with cryptolepine (2.5, 5.0 and 7.5 µM) for 24 h resulted in marked decrease in topoisomerase activity, which was associated with substantial DNA damage as detected by the comet assay. Cryptolepine induced DNA damage resulted in: (i) an increase in the phosphorylation of ATM/ATR, BRCA1, Chk1/Chk2 and γH2AX; (ii) activation of p53 signaling cascade, including enhanced protein expressions of p16 and p21; (iii) downregulation of cyclin-dependent kinases, cyclin D1, cyclin A, cyclin E and proteins involved in cell division (e.g., Cdc25a and Cdc25b) leading to cell cycle arrest at S-phase; and (iv) mitochondrial membrane potential was disrupted and cytochrome c released. These changes in NMSCC by cryptolepine resulted in significant reduction in cell viability, colony formation and increase in apoptotic cell death. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

13 pages, 787 KiB

Open AccessReview

Emerging Phytochemicals for the Prevention and Treatment of Head and Neck Cancer

by Santosh K. Katiyar

Molecules 2016, 21(12), 1610; https://doi.org/10.3390/molecules21121610 - 24 Nov 2016

Cited by 42 | Viewed by 7517

Abstract

Despite the development of more advanced medical therapies, cancer management remains a problem. Head and neck squamous cell carcinoma (HNSCC) is a particularly challenging malignancy and requires more effective treatment strategies and a reduction in the debilitating morbidities associated with the therapies. Phytochemicals [...] Read more.

Despite the development of more advanced medical therapies, cancer management remains a problem. Head and neck squamous cell carcinoma (HNSCC) is a particularly challenging malignancy and requires more effective treatment strategies and a reduction in the debilitating morbidities associated with the therapies. Phytochemicals have long been used in ancient systems of medicine, and non-toxic phytochemicals are being considered as new options for the effective management of cancer. Here, we discuss the growth inhibitory and anti-cell migratory actions of proanthocyanidins from grape seeds (GSPs), polyphenols in green tea and honokiol, derived from the Magnolia species. Studies of these phytochemicals using human HNSCC cell lines from different sub-sites have demonstrated significant protective effects against HNSCC in both in vitro and in vivo models. Treatment of human HNSCC cell lines with GSPs, (−)-epigallocatechin-3-gallate (EGCG), a polyphenolic component of green tea or honokiol reduced cell viability and induced apoptosis. These effects have been associated with inhibitory effects of the phytochemicals on the epidermal growth factor receptor (EGFR), and cell cycle regulatory proteins, as well as other major tumor-associated pathways. Similarly, the cell migration capacity of HNSCC cell lines was inhibited. Thus, GSPs, honokiol and EGCG appear to be promising bioactive phytochemicals for the management of head and neck cancer. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

► Show Figures

Figure 1

21 pages, 923 KiB

Open AccessReview

Multivalent Aptamers: Versatile Tools for Diagnostic and Therapeutic Applications

by Mariya Vorobyeva, Pavel Vorobjev and Alya Venyaminova

Molecules 2016, 21(12), 1613; https://doi.org/10.3390/molecules21121613 - 25 Nov 2016

Cited by 104 | Viewed by 12386

Abstract

Nucleic acid aptamers generated through an in vitro selection are currently extensively applied as very valuable biomolecular tools thanks to their prominent advantages. Diversity of spatial structures, ease of production through chemical synthesis and a large variety of chemical modifications make aptamers convenient [...] Read more.

Nucleic acid aptamers generated through an in vitro selection are currently extensively applied as very valuable biomolecular tools thanks to their prominent advantages. Diversity of spatial structures, ease of production through chemical synthesis and a large variety of chemical modifications make aptamers convenient building blocks for the generation of multifunctional constructs. An opportunity to combine different aptamer functionalities with other molecules of interest such as reporter groups, nanoparticles, chemotherapeutic agents, siRNA or antisense oligonucleotides provides a widest range of applications of multivalent aptamers. The present review summarizes approaches to the design of multivalent aptamers, various examples of multifunctional constructs and the prospects of employing them as components of biosensors, probes for affinity capture, tools for cell research and potential therapeutic candidates. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

► Show Figures

Figure 1

18 pages, 975 KiB

Open AccessReview

Gold Nanoparticles in Single-Cell Analysis for Surface Enhanced Raman Scattering

by Mine Altunbek, Gamze Kuku and Mustafa Culha

Molecules 2016, 21(12), 1617; https://doi.org/10.3390/molecules21121617 - 25 Nov 2016

Cited by 43 | Viewed by 11558

Abstract

The need for new therapeutic approaches in the treatment of challenging diseases such as cancer, which often consists of a highly heterogeneous and complex population of cells, brought up the idea of analyzing single cells. The development of novel techniques to analyze single [...] Read more.

The need for new therapeutic approaches in the treatment of challenging diseases such as cancer, which often consists of a highly heterogeneous and complex population of cells, brought up the idea of analyzing single cells. The development of novel techniques to analyze single cells has been intensively studied to fully understand specific alternations inducing abnormalities in cellular function. One of the techniques used for single cell analysis is surface-enhanced Raman spectroscopy (SERS) in which a noble metal nanoparticle is used to enhance Raman scattering. Due to its low toxicity and biocompatibility, gold nanoparticles (AuNPs) are commonly preferred as SERS substrates in single cell analysis. The intracellular uptake, localization and toxicity issues of AuNPs are the critical points for interpretation of data since the obtained SERS signals originate from molecules in close vicinity to AuNPs that are taken up by the cells. In this review, the AuNP–living cell interactions, cellular uptake and toxicity of AuNPs in relation to their physicochemical properties, and surface-enhanced Raman scattering from single cells are discussed. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Applications)

► Show Figures

Figure 1

15 pages, 572 KiB

Open AccessReview

Antiproliferative Effect of Indole Phytoalexins

by Martina Chripkova, Frantisek Zigo and Jan Mojzis

Molecules 2016, 21(12), 1626; https://doi.org/10.3390/molecules21121626 - 26 Nov 2016

Cited by 74 | Viewed by 10216

Abstract

Indole phytoalexins from crucifers have been shown to exhibit significant anti-cancer, chemopreventive, and antiproliferative activity. Phytoalexins are natural low molecular antimicrobial compounds that are synthesized and accumulated in plants after their exposure to pathogenic microorganisms. Most interestingly, crucifers appear to be the only [...] Read more.

Indole phytoalexins from crucifers have been shown to exhibit significant anti-cancer, chemopreventive, and antiproliferative activity. Phytoalexins are natural low molecular antimicrobial compounds that are synthesized and accumulated in plants after their exposure to pathogenic microorganisms. Most interestingly, crucifers appear to be the only plant family producing sulfur-containing indole phytoalexins. The mechanisms underlying its anti-cancer properties are unknown. Isolation from cruciferous plants does not provide sufficient quantities of indole phytoalexins and, for biological screening, they are usually obtainable through synthesis. Understanding the molecular mechanism of the action of these substances and their structure-activity relationships is quite important in the development of new analogs with a more favorable profile of biological activities. In this review, we present the key features of indole phytoalexins, mainly their antiproliferative ativities. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

► Show Figures

Figure 1

19 pages, 816 KiB

Open AccessReview

Ribosome-Inactivating Proteins from Plants: A Historical Overview

by Andrea Bolognesi, Massimo Bortolotti, Stefania Maiello, Maria Giulia Battelli and Letizia Polito

Molecules 2016, 21(12), 1627; https://doi.org/10.3390/molecules21121627 - 26 Nov 2016

Cited by 95 | Viewed by 10883

Abstract

This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in [...] Read more.

This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development. Full article

(This article belongs to the Special Issue Ribosome-Inactivating Proteins--Commemorative Issue in Honor of Professor Fiorenzo Stirpe)

► Show Figures

Figure 1

27 pages, 5004 KiB

Open AccessReview

Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis

by Yingqian Ci, Jinping Qiao and Mei Han

Molecules 2016, 21(12), 1634; https://doi.org/10.3390/molecules21121634 - 17 Dec 2016

Cited by 51 | Viewed by 11338

Abstract

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options [...] Read more.

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

► Show Figures

Figure 1

20 pages, 1774 KiB

Open AccessReview

Water Will Be the Coal of the Future—The Untamed Dream of Jules Verne for a Solar Fuel

by Vladimir K. Ryabchuk, Vyacheslav N. Kuznetsov, Alexei V. Emeline, Yurii M. Artem’ev, Galina V. Kataeva, Satoshi Horikoshi and Nick Serpone

Molecules 2016, 21(12), 1638; https://doi.org/10.3390/molecules21121638 - 29 Nov 2016

Cited by 20 | Viewed by 6964

Abstract

This article evokes the futuristic visions of two giants, one a writer, Jules Verne, who foresaw water as the coal of the future, and the other a scientist, Giacomo Ciamician, who foresaw the utilization of solar energy as an energy source [...] Read more.

This article evokes the futuristic visions of two giants, one a writer, Jules Verne, who foresaw water as the coal of the future, and the other a scientist, Giacomo Ciamician, who foresaw the utilization of solar energy as an energy source with which to drive photochemical and photocatalytic reactions for the betterment of mankind. Specifically, we examine briefly the early work of the 1960s and 1970s on the photosplitting of free water and water adsorbed on solid supports, based mostly on metal oxides, from which both hydrogen and oxygen evolve in the expected stoichiometric ratio of 2 to 1. The two oil crises of the 1970s (1973 and 1979) spurred the interest of researchers from various disciplines (photochemistry, photo-catalysis and photoelectrochemistry) in search of a Holy Grail photocatalyst, process, or strategy to achieve efficient water splitting so as to provide an energy source alternative to fossil fuels. Some approaches to the photosplitting of water adsorbed on solid insulators (high bandgap materials; E_bg ≥ 5 eV) and semiconductor photocatalysts (metal oxides) are described from which we deduce that metal oxides with bandgap energies around 5 eV (e.g., ZrO₂) are more promising materials to achieve significant water splitting on the basis of quantum yields than narrower bandgap photocatalysts (e.g., TiO₂; E_bg ≈ 3.0–3.2 eV), which tend to be relatively inactive by comparison. Although proof of concept of the photosplitting of water has been demonstrated repeatedly in the last four decades, much remains to be done to find the Holy Grail photocatalyst and/or strategy to achieve significant yields of hydrogen. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

► Show Figures

Graphical abstract

20 pages, 7168 KiB

Open AccessReview

Steric and Stereochemical Modulation in Pyridyl- and Quinolyl-Containing Ligands

by Zhaohua Dai

Molecules 2016, 21(12), 1647; https://doi.org/10.3390/molecules21121647 - 1 Dec 2016

Cited by 7 | Viewed by 5739

Abstract

Nitrogen-containing pyridine and quinoline are outstanding platforms on which excellent ionophores and sensors for metal ions can be built. Steric and stereochemical effects can be used to modulate the affinity and selectivity of such ligands toward different metal ions on the coordination chemistry [...] Read more.

Nitrogen-containing pyridine and quinoline are outstanding platforms on which excellent ionophores and sensors for metal ions can be built. Steric and stereochemical effects can be used to modulate the affinity and selectivity of such ligands toward different metal ions on the coordination chemistry front. On the signal transduction front, such effects can also be used to modulate optical responses of these ligands in metal sensing systems. In this review, steric modulation of achiral ligands and stereochemical modulation in chiral ligands, especially ionophores and sensors for zinc, copper, silver, and mercury, are examined using published structural and spectral data. Although it might be more challenging to construct chiral ligands than achiral ones, isotropic and anisotropic absorption signals from a single chiroptical fluorescent sensor provide not only detection but also differentiation of multiple analytes with high selectivity. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

27 pages, 5175 KiB

Open AccessReview

Phenols and Polyphenols as Carbonic Anhydrase Inhibitors

by Anastasia Karioti, Fabrizio Carta and Claudiu T. Supuran

Molecules 2016, 21(12), 1649; https://doi.org/10.3390/molecules21121649 - 2 Dec 2016

Cited by 87 | Viewed by 11168

Abstract

Phenols are among the largest and most widely distributed groups of secondary metabolites within the plant kingdom. They are implicated in multiple and essential physiological functions. In humans they play an important role as microconstituents of the daily diet, their consumption being considered [...] Read more.

Phenols are among the largest and most widely distributed groups of secondary metabolites within the plant kingdom. They are implicated in multiple and essential physiological functions. In humans they play an important role as microconstituents of the daily diet, their consumption being considered healthy. The physical and chemical properties of phenolic compounds make these molecules versatile ligands, capable of interacting with a wide range of targets, such as the Carbonic Anhydrases (CAs, EC 4.2.1.1). CAs reversibly catalyze the fundamental reaction of CO₂ hydration to bicarbonate and protons in all living organisms, being actively involved in the regulation of a plethora of patho/physiological processes. This review will discuss the most recent advances in the search of naturally occurring phenols and their synthetic derivatives that inhibit the CAs and their mechanisms of action at molecular level. Plant extracts or mixtures are not considered in the present review. Full article

(This article belongs to the Special Issue Carbonic Anhydrase Inhibitors from Natural Products)

► Show Figures

Figure 1

16 pages, 5215 KiB

Open AccessReview

Carbon Nanodots as Peroxidase Nanozymes for Biosensing

by Bhaskar Garg and Tanuja Bisht

Molecules 2016, 21(12), 1653; https://doi.org/10.3390/molecules21121653 - 2 Dec 2016

Cited by 125 | Viewed by 13837

Abstract

‘Nanozymes’, a term coined by Scrimin, Pasquato, and co-workers to describe nanomaterials with enzyme-like characteristics, represent an exciting and emerging research area in the field of artificial enzymes. Indubitably, the last decade has witnessed substantial advancements in the design of a variety of [...] Read more.

‘Nanozymes’, a term coined by Scrimin, Pasquato, and co-workers to describe nanomaterials with enzyme-like characteristics, represent an exciting and emerging research area in the field of artificial enzymes. Indubitably, the last decade has witnessed substantial advancements in the design of a variety of functional nanoscale materials, including metal oxides and carbon-based nanomaterials, which mimic the structures and functions of naturally occurring enzymes. Among these, carbon nanodots (C-dots) or carbon quantum dots (CQDs) offer huge potential due to their unique properties as compared to natural enzymes and/or classical artificial enzymes. In this mini review, we discuss the peroxidase-like catalytic activities of C-dots and their applications in biosensing. The scope intends to cover not only the C-dots but also graphene quantum dots (GQDs), doped C-dots/GQDs, carbon nitride dots, and C-dots/GQDs nanocomposites. Nevertheless, this mini review is designed to be illustrative, not comprehensive. Full article

(This article belongs to the Special Issue Nanozymes and Beyond)

► Show Figures

Graphical abstract

19 pages, 5838 KiB

Open AccessReview

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding

by Lucjan Sobczyk, Dorota Chudoba, Peter M. Tolstoy and Aleksander Filarowski

Molecules 2016, 21(12), 1657; https://doi.org/10.3390/molecules21121657 - 2 Dec 2016

Cited by 36 | Viewed by 7804

Abstract

A review of selected literature data related to intramolecular hydrogen bonding in ortho-hydroxyaryl Schiff bases, ortho-hydroxyaryl ketones, ortho-hydroxyaryl amides, proton sponges and ortho-hydroxyaryl Mannich bases is presented. The paper reports on the application of experimental spectroscopic measurements (IR and [...] Read more.

A review of selected literature data related to intramolecular hydrogen bonding in ortho-hydroxyaryl Schiff bases, ortho-hydroxyaryl ketones, ortho-hydroxyaryl amides, proton sponges and ortho-hydroxyaryl Mannich bases is presented. The paper reports on the application of experimental spectroscopic measurements (IR and NMR) and quantum-mechanical calculations for investigations of the proton transfer processes, the potential energy curves, tautomeric equilibrium, aromaticity etc. Finally, the equilibrium between the intra- and inter-molecular hydrogen bonds in amides is discussed. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

► Show Figures

Figure 1

11 pages, 617 KiB

Open AccessReview

Mechanisms of Body Weight Reduction by Black Tea Polyphenols

by Haibo Pan, Ying Gao and Youying Tu

Molecules 2016, 21(12), 1659; https://doi.org/10.3390/molecules21121659 - 7 Dec 2016

Cited by 84 | Viewed by 15054

Abstract

Obesity is one of the most common nutritional diseases worldwide. This disease causes health problems, such as dyslipidemia, hyperglycemia, hypertension and inflammation. There are drugs used to inhibit obesity. However, they have serious side effects outweighing their beneficial effects. Black tea, commonly referred [...] Read more.

Obesity is one of the most common nutritional diseases worldwide. This disease causes health problems, such as dyslipidemia, hyperglycemia, hypertension and inflammation. There are drugs used to inhibit obesity. However, they have serious side effects outweighing their beneficial effects. Black tea, commonly referred to as “fermented tea”, has shown a positive effect on reducing body weight in animal models. Black tea polyphenols are the major components in black tea which reduce body weight. Black tea polyphenols are more effective than green tea polyphenols. Black tea polyphenols exert a positive effect on inhibiting obesity involving in two major mechanisms: (i) inhibiting lipid and saccharide digestion, absorption and intake, thus reducing calorie intake; and (ii) promoting lipid metabolism by activating AMP-activated protein kinase to attenuate lipogenesis and enhance lipolysis, and decreasing lipid accumulation by inhibiting the differentiation and proliferation of preadipocytes; (iii) blocking the pathological processes of obesity and comorbidities of obesity by reducing oxidative stress. Epidemiological studies of the health relevance between anti-obesity and black tea polyphenols consumption remain to be further investigated. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

► Show Figures

Figure 1

11 pages, 3619 KiB

Open AccessReview

Motion of Adsorbed Nano-Particles on Azobenzene Containing Polymer Films

by Sarah Loebner, Joachim Jelken, Nataraja Sekhar Yadavalli, Elena Sava, Nicolae Hurduc and Svetlana Santer

Molecules 2016, 21(12), 1663; https://doi.org/10.3390/molecules21121663 - 3 Dec 2016

Cited by 12 | Viewed by 6921

Abstract

We demonstrate in situ recorded motion of nano-objects adsorbed on a photosensitive polymer film. The motion is induced by a mass transport of the underlying photoresponsive polymer material occurring during irradiation with interference pattern. The polymer film contains azobenzene molecules that undergo reversible [...] Read more.

We demonstrate in situ recorded motion of nano-objects adsorbed on a photosensitive polymer film. The motion is induced by a mass transport of the underlying photoresponsive polymer material occurring during irradiation with interference pattern. The polymer film contains azobenzene molecules that undergo reversible photoisomerization reaction from trans- to cis-conformation. Through a multi-scale chain of physico-chemical processes, this finally results in the macro-deformations of the film due to the changing elastic properties of polymer. The topographical deformation of the polymer surface is sensitive to a local distribution of the electrical field vector that allows for the generation of dynamic changes in the surface topography during irradiation with different light interference patterns. Polymer film deformation together with the motion of the adsorbed nano-particles are recorded using a homemade set-up combining an optical part for the generation of interference patterns and an atomic force microscope for acquiring the surface deformation. The particles undergo either translational or rotational motion. The direction of particle motion is towards the topography minima and opposite to the mass transport within the polymer film. The ability to relocate particles by photo-induced dynamic topography fluctuation offers a way for a non-contact simultaneous manipulation of a large number of adsorbed particles just in air at ambient conditions. Full article

(This article belongs to the Special Issue Photoresponsive Polymers)

► Show Figures

Figure 1

33 pages, 514 KiB

Open AccessReview

Chemical Variability and Biological Activities of Eucalyptus spp. Essential Oils

by Luiz Claudio Almeida Barbosa, Claudinei Andrade Filomeno and Robson Ricardo Teixeira

Molecules 2016, 21(12), 1671; https://doi.org/10.3390/molecules21121671 - 7 Dec 2016

Cited by 189 | Viewed by 21915

Abstract

Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than [...] Read more.

Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than 3000 EOs reported in the literature, with approximately 300 in commercial use, including the EOs from Eucalyptus species. Most EOs from Eucalyptus species are rich in monoterpenes and many have found applications in pharmaceuticals, agrochemicals, food flavorants, and perfumes. Such applications are related to their diverse biological and organoleptic properties. In this study, we review the latest information concerning the chemical composition and biological activities of EOs from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus, we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricidal, insecticidal and herbicidal activities, hoping that such information will contribute to the development of research in this field. It is also intended that the information described in this study can be useful in the rationalization of the use of Eucalyptus EOs as components for pharmaceutical and agrochemical applications as well as food preservatives and flavorants. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

► Show Figures

Graphical abstract

19 pages, 732 KiB

Open AccessReview

Cancer Preventive Activities of Tea Catechins

by Chung S. Yang and Hong Wang

Molecules 2016, 21(12), 1679; https://doi.org/10.3390/molecules21121679 - 9 Dec 2016

Cited by 180 | Viewed by 14100

Abstract

Catechins are widely occurring in our diet and beverages. The cancer-preventive activities of catechins have been extensively studied. Of these, (−)-epigallocatechin-3-gallate (EGCG), the principal catechin in green tea, has received the most attention. The inhibitory activities of tea catechins against carcinogenesis and cancer [...] Read more.

Catechins are widely occurring in our diet and beverages. The cancer-preventive activities of catechins have been extensively studied. Of these, (−)-epigallocatechin-3-gallate (EGCG), the principal catechin in green tea, has received the most attention. The inhibitory activities of tea catechins against carcinogenesis and cancer cell growth have been demonstrated in a large number of laboratory studies. Many mechanisms for modulating cancer signaling and metabolic pathways have been proposed based on numerous studies in cell lines with EGCG, the most active tea catechin. Nevertheless, it is not known whether many of these mechanisms indeed contribute to the anti-cancer activities in animals and in humans. Human studies have provided some results for the cancer preventive activities of tea catechins; however, the activities are not strong. This article reviews the cancer preventive activities and mechanisms of action of tea catechins involving their redox activities, biochemical properties and binding to key enzymes or signal transduction proteins. These mechanisms lead to suppression of cell proliferation, increased apoptosis and inhibition of angiogenesis. The relevance of the proposed mechanisms for cancer prevention are assessed in the light of the situation in vivo. The potential and possible problems in the application of tea and tea-derived products for cancer prevention are discussed. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

► Show Figures

Figure 1

11 pages, 226 KiB

Open AccessReview

Black Crowberry (Empetrum nigrum L.) Flavonoids and Their Health Promoting Activity

by Tunde Jurikova, Jiri Mlcek, Sona Skrovankova, Stefan Balla, Jiri Sochor, Mojmir Baron and Daniela Sumczynski

Molecules 2016, 21(12), 1685; https://doi.org/10.3390/molecules21121685 - 7 Dec 2016

Cited by 42 | Viewed by 8958

Abstract

Nowadays, much research attention is focused on underutilized berry crops due to the high antioxidant activity of fruits. Black crowberry (Empetrum nigrum L.) represents an important source of flavonols (quercetin, rutin, myricetin, naringenin, naringin, morin, and kaempferol) and anthocyanins. The fruit components [...] Read more.

Nowadays, much research attention is focused on underutilized berry crops due to the high antioxidant activity of fruits. Black crowberry (Empetrum nigrum L.) represents an important source of flavonols (quercetin, rutin, myricetin, naringenin, naringin, morin, and kaempferol) and anthocyanins. The fruit components could be utilised as natural colourants or as a part of functional foods and, because of the high antioxidant activity, the berries of black crowberry can be used in the treatment of diseases accompanied with inflammation, or as an effective antibacterial and antifungal remedy. Moreover, the reduction of lipid accumulation and total cholesterol as well as an improvement of postprandial hyperglycaemia have been proven. This review summarizes for the first time the main antioxidants (flavonoids) of black crowberry fruits, with a focus on their health promoting activity. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

16 pages, 1466 KiB

Open AccessReview

A Review on Phytochemistry and Pharmacology of Cortex Periplocae

by Yang Li, Jin Li, Kun Zhou, Jun He, Jun Cao, Mingrui An and Yan-Xu Chang

Molecules 2016, 21(12), 1702; https://doi.org/10.3390/molecules21121702 - 10 Dec 2016

Cited by 29 | Viewed by 6884

Abstract

Cortex Periplocae, as a traditional Chinese herbal medicine, has been widely used for autoimmune diseases, especially rheumatoid arthritis. Due to its potential pharmaceutical values, more studies about the biological activities of Cortex Periplocae have been conducted recently. Meanwhile, the adverse reaction of [...] Read more.

Cortex Periplocae, as a traditional Chinese herbal medicine, has been widely used for autoimmune diseases, especially rheumatoid arthritis. Due to its potential pharmaceutical values, more studies about the biological activities of Cortex Periplocae have been conducted recently. Meanwhile, the adverse reaction of Cortex Periplocae is not a negligible problem in clinic. In this article, we reviewed a series of articles and summarized the recent studies of Cortex Periplocae in the areas of phytochemistry and pharmacology. More than 100 constituents have been isolated and identified from Cortex Periplocae, including steroids, cardiac glycosides, terpenoids, and fatty acid compounds. The crude extracts of Cortex Periplocae and its active compounds exhibit various biological activities, such as cardiotonic effect, anticancer action, and anti-inflammatory effect. This paper aims to provide an overall review on the bioactive ingredients, pharmacological effect, and toxicity of this plant. Furthermore, this review suggests investigating and developing new clinical usages according to the above pharmacological effects. Full article

► Show Figures

Graphical abstract

23 pages, 909 KiB

Open AccessReview

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity

by Yun Chen, Fangke Yao, Ke Ming, Deyun Wang, Yuanliang Hu and Jiaguo Liu

Molecules 2016, 21(12), 1705; https://doi.org/10.3390/molecules21121705 - 13 Dec 2016

Cited by 197 | Viewed by 16934

Abstract

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from [...] Read more.

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development. Full article

► Show Figures

Figure 1

22 pages, 7897 KiB

Open AccessReview

Natural Terpenes as Penetration Enhancers for Transdermal Drug Delivery

by Jun Chen, Qiu-Dong Jiang, Ya-Ping Chai, Hui Zhang, Pei Peng and Xi-Xiong Yang

Molecules 2016, 21(12), 1709; https://doi.org/10.3390/molecules21121709 - 11 Dec 2016

Cited by 164 | Viewed by 12129

Abstract

The greatest hindrance for transdermal drug delivery (TDD) is the barrier property of skin, especially the stratum corneum (SC). Various methodologies have been investigated and developed to enhance the penetration of drugs through the skin. Among them, the most popular approach is the [...] Read more.

The greatest hindrance for transdermal drug delivery (TDD) is the barrier property of skin, especially the stratum corneum (SC). Various methodologies have been investigated and developed to enhance the penetration of drugs through the skin. Among them, the most popular approach is the application of penetration enhancers (PEs), including natural terpenes, a very safe and effective class of PEs. In the present paper, we focused on terpenes as skin PEs for TDD. The mechanism of their action, the factors affecting their penetration enhancement effect, as well as their possible skin toxicity were discussed. Terpenes abundant in nature have great potential in the development of PEs. Compared to synthetic PEs, natural terpenes have been proved to possess higher enhancement activity. Interaction with SC intercellular lipids is the main mechanism of action for terpenes. The key factor affecting the enhancement effect is the lipophilicity of both terpenes and drug molecules. In addition, a lot of terpenes have also been proved to be much less toxic compared to azone, the classic synthetic PE. In summary, terpenes may be preferred over the chemically synthesized compounds as safe and effective PEs to promote the percutaneous absorption of drugs. Full article

30 pages, 1852 KiB

Open AccessReview

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

by Chendi Ding, Ling Tong, Jing Feng and Jiajun Fu

Molecules 2016, 21(12), 1715; https://doi.org/10.3390/molecules21121715 - 20 Dec 2016

Cited by 147 | Viewed by 14524

Abstract

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can [...] Read more.

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

► Show Figures

Graphical abstract

15 pages, 1422 KiB

Open AccessReview

Antibiofilm Activity of Plant Polyphenols

by Lívia Slobodníková, Silvia Fialová, Katarína Rendeková, Ján Kováč and Pavel Mučaji

Molecules 2016, 21(12), 1717; https://doi.org/10.3390/molecules21121717 - 13 Dec 2016

Cited by 224 | Viewed by 16613

Abstract

In the history of human medicine, antibiotics represent epochal examples of medical progress. However, with an approaching antibiotic crisis due to the emergence and extensive spread of antimicrobial resistance among bacterial agents, as well as to increasing number of patients with chronic and [...] Read more.

In the history of human medicine, antibiotics represent epochal examples of medical progress. However, with an approaching antibiotic crisis due to the emergence and extensive spread of antimicrobial resistance among bacterial agents, as well as to increasing number of patients with chronic and recalcitrant bacterial biofilm-associated infections, the naturally occurring molecules may become new sources of antibacterial and antibiofilm drugs for clinical usage. Polyphenols represent a class of plant natural products which are important in plant defense against microbial pathogens. The main focus of the review is on the antibiofilm activities of phenolic compounds against bacteria which play an essential role in medical device biofilm-associated infections. The other, not negligible part of the review is devoted to polyphenols’ activity against bacterial agents that cause dental caries and periodontal disease. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

► Show Figures

Figure 1

17 pages, 593 KiB

Open AccessReview

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

by Brian C. Palmer and Lisa A. DeLouise

Molecules 2016, 21(12), 1719; https://doi.org/10.3390/molecules21121719 - 15 Dec 2016

Cited by 233 | Viewed by 20796

Abstract

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to [...] Read more.

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. Full article

(This article belongs to the Special Issue Transdermal Delivery Systems: Current Landscape and Trends)

► Show Figures

Figure 1

10 pages, 2156 KiB

Open AccessReview

Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation

by Shingo Kasamatsu, Akira Nishimura, Masanobu Morita, Tetsuro Matsunaga, Hisyam Abdul Hamid and Takaaki Akaike

Molecules 2016, 21(12), 1721; https://doi.org/10.3390/molecules21121721 - 15 Dec 2016

Cited by 80 | Viewed by 13241

Abstract

For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur [...] Read more.

For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur transfer system involving CysSSH evidently generates glutathione persulfide (GSSH) that exists at concentrations greater than 100 μM in vivo. Because reactive persulfide species such as CysSSH and GSSH have higher nucleophilicity than parental cysteine (Cys) and glutathione do, these reactive species exhibit strong scavenging activities against oxidants, e.g., hydrogen peroxide, and electrophiles, which contributes to redox signaling regulation. Also, several papers indicated that various proteins and enzymes have Cys polysulfides including CysSSH at their specific Cys residues, which is called protein polysulfidation. Apart from the redox signaling regulatory mechanism, another plausible function of protein polysulfidation is providing protection for protein thiol residues against irreversible chemical modification caused by oxidants and electrophiles. Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

► Show Figures

Figure 1

10 pages, 2409 KiB

Open AccessReview

Polyamines and α-Carbonic Anhydrases

by Andrea Scozzafava, Claudiu T. Supuran and Fabrizio Carta

Molecules 2016, 21(12), 1726; https://doi.org/10.3390/molecules21121726 - 15 Dec 2016

Cited by 11 | Viewed by 6256

Abstract

Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the [...] Read more.

Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1). CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS)-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs. Full article

(This article belongs to the Special Issue Carbonic Anhydrase Inhibitors from Natural Products)

► Show Figures

Figure 1

15 pages, 725 KiB

Open AccessReview

The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate

by Paweł Lis, Mariusz Dyląg, Katarzyna Niedźwiecka, Young H. Ko, Peter L. Pedersen, Andre Goffeau and Stanisław Ułaszewski

Molecules 2016, 21(12), 1730; https://doi.org/10.3390/molecules21121730 - 15 Dec 2016

Cited by 170 | Viewed by 23535

Abstract

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the [...] Read more.

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Figure 1

12 pages, 222 KiB

Open AccessReview

The Health Benefiting Mechanisms of Virgin Olive Oil Phenolic Compounds

by Lisa Parkinson and Sara Cicerale

Molecules 2016, 21(12), 1734; https://doi.org/10.3390/molecules21121734 - 16 Dec 2016

Cited by 160 | Viewed by 15159

Abstract

Virgin olive oil (VOO) is credited as being one of the many healthful components associated with the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday Mediterranean dietary pattern. VOO [...] Read more.

Virgin olive oil (VOO) is credited as being one of the many healthful components associated with the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday Mediterranean dietary pattern. VOO is rich in phenolic compounds and the health promoting benefits of these phenolics are now established. Recent studies have highlighted the biological properties of VOO phenolic compounds elucidating their anti-inflammatory activities. This paper will review current knowledge on the anti-inflammatory and nutrigenomic, chemoprotective and anti-atherosclerotic activities of VOO phenolics. In addition the concentration, metabolism and bioavailability of specific phenolic compounds will be discussed. The evidence presented in the review concludes that oleurepein, hydroxytyrosol and oleocanthal have potent pharmacological activities in vitro and in vivo; however, intervention studies with biologically relevant concentrations of these phenolic compounds are required. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

19 pages, 1208 KiB

Open AccessReview

A Review of the Botany, Phytochemistry, Pharmacology and Toxicology of Rubiae Radix et Rhizoma

by Mingqiu Shan, Sheng Yu, Hui Yan, Peidong Chen, Li Zhang and Anwei Ding

Molecules 2016, 21(12), 1747; https://doi.org/10.3390/molecules21121747 - 20 Dec 2016

Cited by 44 | Viewed by 9559

Abstract

Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, [...] Read more.

Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, swelling and pain caused by injuries from falls. In addition, it is a kind of pigment utilized as a food additive and a dye for wool or fiber. This review mainly concentrates on studies of the botany, phytochemistry, pharmacology and toxicology of this Traditional Chinese Medicine. The phytochemical evidences indicated that over a hundred chemical components have been found and isolated from the medicine, such as anthraquinones, naphthoquinones, triterpenoids, cyclic hexapeptides and others. These components are considered responsible for the various bioactivities of the herbal drug, including anti-oxidation, anti-inflammation, immunomodulation, antitumor, effects on coagulation-fibrinolysis system, neuroprotection and other effects. Additionally, based on these existing results, we also propose some interesting future research directions. Consequently, this review should help us to more comprehensively understand and to more fully utilize the herbal medicine Rubiae Radix et Rhizoma. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Graphical abstract

22 pages, 1510 KiB

Open AccessReview

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

by Caroline Coisne, Sébastien Tilloy, Eric Monflier, Daniel Wils, Laurence Fenart and Fabien Gosselet

Molecules 2016, 21(12), 1748; https://doi.org/10.3390/molecules21121748 - 20 Dec 2016

Cited by 102 | Viewed by 13840

Abstract

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the [...] Read more.

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE^® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer’s, Parkinson’s and Huntington’s diseases are currently on-going. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

► Show Figures

Figure 1

12 pages, 1618 KiB

Open AccessReview

Sulfur Atom in its Bound State Is a Unique Element Involved in Physiological Functions in Mammals

by Shin Koike and Yuki Ogasawara

Molecules 2016, 21(12), 1753; https://doi.org/10.3390/molecules21121753 - 21 Dec 2016

Cited by 33 | Viewed by 8616

Abstract

It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, [...] Read more.

It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, sulfane sulfur is described as sulfur atoms that are covalently bound only with sulfur atoms, and as this explanation was somewhat difficult to comprehend, it was not generally accepted. Thus, in the early 1990s, we redefined these sulfur species as “bound sulfur”, which easily converts to hydrogen sulfide on reduction with a thiol reducing agent. In other words, bound sulfur refers to a sulfur atom that exists in a zero to divalent form (0 to −2). The first part of this review focuses on the fluorescent derivatization HPLC method—which we developed for measurement of bound sulfur—and explains the distribution of bound sulfur and the hydrogen sulfide-producing ability of various tissues, as clarified by this method. Next, we discuss diverse physiological functions and involvement of polysulfide, a typical type of bound sulfur, in the redox regulation system. Additionally, we also address its possible physiological role in the central nervous system, based on its action of scavenging reactive carbonyl compounds. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

► Show Figures

Figure 1

7 pages, 476 KiB

Open AccessReview

Preventive Effects of Catechins on Cardiovascular Disease

by Xiao-Qiang Chen, Ting Hu, Yu Han, Wei Huang, Hai-Bo Yuan, Yun-Tian Zhang, Yu Du and Yong-Wen Jiang

Molecules 2016, 21(12), 1759; https://doi.org/10.3390/molecules21121759 - 21 Dec 2016

Cited by 86 | Viewed by 8819

Abstract

Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the [...] Read more.

Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

1 pages, 141 KiB

Open AccessErratum

Erratum: Pferschy-Wenzig, E.-M.; et al. Does a Graphical Abstract Bring More Visibility to Your Paper? Molecules 2016, 21, 1247

by Eva-Maria Pferschy-Wenzig, Ulrich Pferschy, Dongdong Wang, Andrei Mocan and Atanas G. Atanasov

Molecules 2016, 21(12), 1676; https://doi.org/10.3390/molecules21121676 - 6 Dec 2016

Cited by 2 | Viewed by 3785

Abstract

The authors wish to make the following change to their paper [1].[...] Full article

2 pages, 5973 KiB

Open AccessCorrection

Correction: Zhao, J., et al. Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies. Molecules 2016, 21, 1549

by Jihui Zhao, Xianghua Piao, Xiaoqin Shi, Aiyong Si, Yongtai Zhang and Nianping Feng

Molecules 2016, 21(12), 1695; https://doi.org/10.3390/molecules21121695 - 9 Dec 2016

Cited by 1 | Viewed by 3838

Abstract

The authors wish to make the following correction to their paper [1]. Full article

► Show Figures

Figure 4

Journal Menu

Journal Browser

Molecules, Volume 21, Issue 12 (December 2016) – 153 articles

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI