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Molecules, Volume 20, Issue 7 (July 2015), Pages 11632-13495

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Editorial

Jump to: Research, Review

Open AccessEditorial Special Issue—Towards Understanding the Mechanisms and Curing of Muscular Dystrophy Diseases
Molecules 2015, 20(7), 12944-12945; doi:10.3390/molecules200712944
Received: 14 July 2015 / Accepted: 16 July 2015 / Published: 16 July 2015
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Abstract
Muscular dystrophies are a heterogeneous group of inherited diseases with different molecular basss, but sharing similar clinical features and dystrophic changes. Full article

Research

Jump to: Editorial, Review

Open AccessArticle Anion Recognition by Pyrylium Cations and Thio-, Seleno- and Telluro- Analogues: A Combined Theoretical and Cambridge Structural Database Study
Molecules 2015, 20(7), 11632-11659; doi:10.3390/molecules200711632
Received: 5 June 2015 / Revised: 17 June 2015 / Accepted: 18 June 2015 / Published: 24 June 2015
Cited by 5 | PDF Full-text (3461 KB) | HTML Full-text | XML Full-text
Abstract
Pyrylium salts are a very important class of organic molecules containing a trivalent oxygen atom in a six-membered aromatic ring. In this manuscript, we report a theoretical study of pyrylium salts and their thio-, seleno- and telluro- analogues by means of DFT calculations.
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Pyrylium salts are a very important class of organic molecules containing a trivalent oxygen atom in a six-membered aromatic ring. In this manuscript, we report a theoretical study of pyrylium salts and their thio-, seleno- and telluro- analogues by means of DFT calculations. For this purpose, unsubstituted 2,4,6-trimethyl and 2,4,6-triphenyl cations and anions with different morphologies were chosen (Cl, NO3 and BF4). The complexes were characterized by means of natural bond orbital and “atoms-in-molecules” theories, and the physical nature of the interactions has been analyzed by means of symmetry-adapted perturbation theory calculations. Our results indicate the presence of anion-π interactions and chalcogen bonds based on both σ- and π-hole interactions and the existence of very favorable σ-complexes, especially for unsubstituted cations. The electrostatic component is dominant in the interactions, although the induction contributions are important, particularly for chloride complexes. The geometrical features of the complexes have been compared with experimental data retrieved from the Cambridge Structural Database. Full article
(This article belongs to the Special Issue Noncovalent pi-Interactions)
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Open AccessArticle Antibacterial Activity and Mechanism of Action of Sulfone Derivatives Containing 1,3,4-Oxadiazole Moieties on Rice Bacterial Leaf Blight
Molecules 2015, 20(7), 11660-11675; doi:10.3390/molecules200711660
Received: 29 April 2015 / Revised: 4 June 2015 / Accepted: 12 June 2015 / Published: 24 June 2015
Cited by 4 | PDF Full-text (903 KB) | HTML Full-text | XML Full-text
Abstract
In this study, sulfone derivatives containing 1,3,4-oxadiazole moieties indicated good antibacterial activities against rice bacterial leaf blight caused by the pathogen Xanthomonas oryzaepv. pv. oryzae (Xoo). In particular, 2-(methylsulfonyl)-5-(4-fluorobenzyl)-1,3,4-oxadiazole revealed the best antibacterial activity against Xoo, with a half-maximal effective
[...] Read more.
In this study, sulfone derivatives containing 1,3,4-oxadiazole moieties indicated good antibacterial activities against rice bacterial leaf blight caused by the pathogen Xanthomonas oryzaepv. pv. oryzae (Xoo). In particular, 2-(methylsulfonyl)-5-(4-fluorobenzyl)-1,3,4-oxadiazole revealed the best antibacterial activity against Xoo, with a half-maximal effective concentration (EC50) of 9.89 μg/mL, which was better than those of the commercial agents of bismerthiazole (92.61 μg/mL) and thiodiazole copper (121.82 μg/mL). In vivo antibacterial activity tests under greenhouse conditions and field trials demonstrated that 2-(methylsulfonyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole was effective in reducing rice bacterial leaf blight. Meanwhile, 2-(methylsulfonyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole stimulate the increase in superoxide dismutase (SOD) and peroxidase (POD) activities in rice, causing marked enhancement of plant resistance against rice bacterial leaf blight. It could also improve the chlorophyll content and restrain the increase in the malondialdehyde (MDA) content in rice to considerably reduce the amount of damage caused by Xoo. Moreover, 2-(methylsulfonyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole, at a concentration of 20 μg/mL, could inhibit the production of extracellular polysaccharide (EPS) with an inhibition ratio of 94.52%, and reduce the gene expression levels of gumB, gumG, gumM, and xanA, with inhibition ratios of 94.88%, 68.14%, 86.76%, and 79.21%, respectively. Full article
Open AccessArticle Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity
Molecules 2015, 20(7), 11676-11698; doi:10.3390/molecules200711676
Received: 2 June 2015 / Revised: 17 June 2015 / Accepted: 19 June 2015 / Published: 25 June 2015
Cited by 7 | PDF Full-text (1008 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para-
[...] Read more.
Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para- position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group. Full article
(This article belongs to the Special Issue C-H Bond Activation and Functionalization)
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Open AccessArticle Redox-Active Profile Characterization of Remirea maritima Extracts and Its Cytotoxic Effect in Mouse Fibroblasts (L929) and Melanoma (B16F10) Cells
Molecules 2015, 20(7), 11699-11718; doi:10.3390/molecules200711699
Received: 8 December 2014 / Revised: 6 May 2015 / Accepted: 12 May 2015 / Published: 25 June 2015
Cited by 5 | PDF Full-text (922 KB) | HTML Full-text | XML Full-text
Abstract
Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima’s biological actions are available and there are no reports regarding the redox-active
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Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima’s biological actions are available and there are no reports regarding the redox-active profile of this plant. In this study, we examined the total phenolic content of Remirea maritima hydroalcoholic (RMHA) extracts, redox properties against different reactive species generated in vitro and their cytotoxic effect against fibroblasts (L929) and melanoma (B16F10) cells. Total reactive antioxidant potential index (TRAP) and total antioxidant reactivity (TAR) results revealed that RMHA at all concentrations tested showed significant antioxidant capacity. RMHA was also effective against hydroxyl radical formation, reduction of Fe3+ to Fe2+ and in scavenging nitric oxide (NO) radicals. In vitro, the level of lipid peroxidation was reduced by RMHA extract and the data showed significant oxidative damage protection. The RMHA cytotoxicity was evaluated by a neutral red assay in fibroblast (L929) and melanome (B16F10) cells. The obtained results showed that the RMHA (40 and 80 µg/mL, respectively) reduced 70% of the viable cells. In conclusion, this study represents the first report regarding the antioxidant and anti-proliferative potential of R. maritima against B16F10 melanoma cells. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer—An in Vitro Model for Blood-Brain Barrier Permeability
Molecules 2015, 20(7), 11719-11732; doi:10.3390/molecules200711719
Received: 16 May 2015 / Revised: 19 June 2015 / Accepted: 23 June 2015 / Published: 25 June 2015
Cited by 7 | PDF Full-text (1081 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2
[...] Read more.
Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples’ transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp) were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp) inhibitor (verapamil) experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5) and log D (at pH 7.4) were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
Open AccessArticle A Multi-Target Approach toward the Development of Novel Candidates for Antidermatophytic Activity: Ultrastructural Evidence on α-Bisabolol-Treated Microsporum gypseum
Molecules 2015, 20(7), 11765-11776; doi:10.3390/molecules200711765
Received: 8 May 2015 / Revised: 22 June 2015 / Accepted: 24 June 2015 / Published: 26 June 2015
Cited by 4 | PDF Full-text (1271 KB) | HTML Full-text | XML Full-text
Abstract
Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated,
[...] Read more.
Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. α-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by α-bisabolol by TEM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Anemarrhena asphodeloides Non-Steroidal Saponin Components Alter the Pharmacokinetic Profile of Its Steroidal Saponins in Rat
Molecules 2015, 20(7), 11777-11792; doi:10.3390/molecules200711777
Received: 13 May 2015 / Revised: 12 June 2015 / Accepted: 22 June 2015 / Published: 26 June 2015
Cited by 2 | PDF Full-text (1533 KB) | HTML Full-text | XML Full-text
Abstract
A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small
[...] Read more.
A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small molecule fraction (ASE-SF) and ASE combined with small molecule and macromolecular fraction (ASE-SF-MF) containing approximately the same dose of ASE. At different time points, the concentration of timosaponin BII, anemarsaponin BIII, timosaponin AIII and timosaponin E1 in rat plasma were determined and main pharmacokinetic parameters including Cmax, Tmax, T1/2, AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student’s t-test with p < 0.05 as the level of significance. MF had no effect on the pharmacokinetic behaviors and parameters of four steroidal saponins. It was found that Cmax and AUC of four steroidal saponins in group ASE-SF and ASE-SF-MF, were significantly increased compared with those in group ASE. These results indicate that SF in A. asphodeloides extracts could increase the absorption and improve the bioavailability of the steroidal saponins. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Inhibition of Tapeworm Thioredoxin and Glutathione Pathways by an Oxadiazole N-Oxide Leads to Reduced Mesocestoides vogae Infection Burden in Mice
Molecules 2015, 20(7), 11793-11807; doi:10.3390/molecules200711793
Received: 20 March 2015 / Revised: 14 June 2015 / Accepted: 18 June 2015 / Published: 26 June 2015
Cited by 1 | PDF Full-text (1457 KB) | HTML Full-text | XML Full-text
Abstract
Parasitic flatworms cause serious infectious diseases that affect humans and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising
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Parasitic flatworms cause serious infectious diseases that affect humans and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising pharmacological target. We purified to homogeneity and characterized the TGR from the tapeworm Mesocestoides vogae (syn. M. corti). This purification revealed absence of conventional TR and GR. The glutathione reductase activity of the purified TGR exhibits a hysteretic behavior typical of flatworm TGRs. Consistently, M. vogae genome analysis revealed the presence of a selenocysteine-containing TGR and absence of conventional TR and GR. M. vogae thioredoxin and glutathione reductase activities were inhibited by 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole N2-oxide (VL16E), an oxadiazole N-oxide previously identified as an inhibitor of fluke and tapeworm TGRs. Finally, we show that mice experimentally infected with M. vogae tetrathyridia and treated with either praziquantel, the reference drug for flatworm infections, or VL16E exhibited a 28% reduction of intraperitoneal larvae numbers compared to vehicle treated mice. Our results show that oxadiazole N-oxide is a promising chemotype in vivo and highlights the convenience of M. vogae as a model for rapid assessment of tapeworm infections in vivo. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
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Open AccessArticle The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene β-Caryophyllene from the Essential Oil of Aquilaria crassna
Molecules 2015, 20(7), 11808-11829; doi:10.3390/molecules200711808
Received: 24 February 2015 / Revised: 20 April 2015 / Accepted: 24 April 2015 / Published: 26 June 2015
Cited by 40 | PDF Full-text (7210 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its
[...] Read more.
The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti-oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of β-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of β-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that β-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 ± 1.0 µM) and more pronounced anti-fungal activity than kanamycin. β-Caryophyllene also displayed strong antioxidant effects. Additionally, β-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 µM). The results also showed that β-caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, β-caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells
Molecules 2015, 20(7), 11830-11860; doi:10.3390/molecules200711830
Received: 2 June 2015 / Accepted: 16 June 2015 / Published: 29 June 2015
Cited by 5 | PDF Full-text (2790 KB) | HTML Full-text | XML Full-text
Abstract
In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher
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In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety
Molecules 2015, 20(7), 11861-11874; doi:10.3390/molecules200711861
Received: 21 April 2015 / Revised: 15 June 2015 / Accepted: 16 June 2015 / Published: 29 June 2015
Cited by 17 | PDF Full-text (1263 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M
[...] Read more.
A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50) values of 138.1 and 154.8 μg/mL, respectively, which were superior to that of Ribavirin (436.0 μg/mL). The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR) of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR) method of comparative molecular field analysis (CoMFA) based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST) experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP). Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Investigations on Synperiplanar and Antiperiplanar Isomers of Losartan: Theoretical and Experimental NMR Studies
Molecules 2015, 20(7), 11875-11890; doi:10.3390/molecules200711875
Received: 31 May 2015 / Revised: 18 June 2015 / Accepted: 23 June 2015 / Published: 29 June 2015
Cited by 5 | PDF Full-text (1876 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Losartan inhibits the renin-angiotensin-aldosterone system by blocking the angiotensin II receptor. It is commonly used in cardiovascular diseases, such as hypertension. Several publications applied the ab initio and density functional theory methods to investigate the molecule of losartan. Only in one of them
[...] Read more.
Losartan inhibits the renin-angiotensin-aldosterone system by blocking the angiotensin II receptor. It is commonly used in cardiovascular diseases, such as hypertension. Several publications applied the ab initio and density functional theory methods to investigate the molecule of losartan. Only in one of them were the nuclear magnetic resonance spectra calculations carried out, and their results were correlated with the experimental values. The authors focused their attention on calculations of the anion form of losartan, taking into consideration both its synperiplanar and antiperiplanar configurations. Coefficients of determination and mean absolute deviation parameters were calculated for the experimental and calculated chemical shifts for every used basis set. They showed a noticeably stronger correlation for the anti-isomers than for the syn-isomers. Moreover, the solvation model increased the value of this parameter. The results of calculations confirmed that an anti-conformation of the analyte seems to be the preferred one, and such an orientation might be most potent within the receptor cavity, which is in agreement with the results of previous studies. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Culture Condition Optimization and Pilot Scale Production of the M12 Metalloprotease Myroilysin Produced by the Deep-Sea Bacterium Myroides profundi D25
Molecules 2015, 20(7), 11891-11901; doi:10.3390/molecules200711891
Received: 8 May 2015 / Revised: 19 June 2015 / Accepted: 23 June 2015 / Published: 29 June 2015
Cited by 4 | PDF Full-text (3163 KB) | HTML Full-text | XML Full-text
Abstract
The protease myroilysin is the most abundant protease secreted by marine sedimental bacterium Myroides profundi D25. As a novel elastase of the M12 family, myroilysin has high elastin-degrading activity and strong collagen-swelling ability, suggesting its promising biotechnological potential. Because myroilysin cannot be maturely
[...] Read more.
The protease myroilysin is the most abundant protease secreted by marine sedimental bacterium Myroides profundi D25. As a novel elastase of the M12 family, myroilysin has high elastin-degrading activity and strong collagen-swelling ability, suggesting its promising biotechnological potential. Because myroilysin cannot be maturely expressed in Escherichia coli, it is important to be able to improve the production of myroilysin in the wild strain D25. We optimized the culture conditions of strain D25 for protease production by using single factor experiments. Under the optimized conditions, the protease activity of strain D25 reached 1137 ± 53.29 U/mL, i.e., 174% of that before optimization (652 ± 23.78 U/mL). We then conducted small scale fermentations of D25 in a 7.5 L fermentor. The protease activity of strain D25 in small scale fermentations reached 1546.4 ± 82.65 U/mL after parameter optimization. Based on the small scale fermentation results, we further conducted pilot scale fermentations of D25 in a 200 L fermentor, in which the protease production of D25 reached approximately 1100 U/mL. These results indicate that we successfully set up the small and pilot scale fermentation processes of strain D25 for myroilysin production, which should be helpful for the industrial production of myroilysin and the development of its biotechnological potential. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ambiphilic Frustrated Lewis Pair Exhibiting High Robustness and Reversible Water Activation: Towards the Metal-Free Hydrogenation of Carbon Dioxide
Molecules 2015, 20(7), 11902-11914; doi:10.3390/molecules200711902
Received: 21 April 2015 / Revised: 4 June 2015 / Accepted: 19 June 2015 / Published: 29 June 2015
Cited by 8 | PDF Full-text (1069 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and structural characterization of a phenylene-bridged Frustrated Lewis Pair (FLP) having a 2,2,6,6‑tetramethylpiperidine (TMP) as the Lewis base and a 9-borabicyclo[3.3.1]nonane (BBN) as the Lewis acid is reported. This FLP exhibits unique robustness towards the products of carbon dioxide hydrogenation. The
[...] Read more.
The synthesis and structural characterization of a phenylene-bridged Frustrated Lewis Pair (FLP) having a 2,2,6,6‑tetramethylpiperidine (TMP) as the Lewis base and a 9-borabicyclo[3.3.1]nonane (BBN) as the Lewis acid is reported. This FLP exhibits unique robustness towards the products of carbon dioxide hydrogenation. The compound shows reversible splitting of water, formic acid and methanol while no reaction is observed in the presence of excess formaldehyde. The molecule is incredibly robust, showing little sign of degradation after heating at 80 °C in benzene with 10 equiv. of formic acid for 24 h. The robustness of the system could be exploited in the design of metal-free catalysts for the hydrogenation of carbon dioxide. Full article
(This article belongs to the Special Issue The Reactivity of Frustrated Lewis Pairs)
Open AccessArticle Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats
Molecules 2015, 20(7), 11915-11929; doi:10.3390/molecules200711915
Received: 8 June 2015 / Revised: 18 June 2015 / Accepted: 22 June 2015 / Published: 30 June 2015
Cited by 3 | PDF Full-text (3676 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Shenfu decoction (SFD) can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF). We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF–MS)-based metabolomic study to increase the understanding of CHF and assess
[...] Read more.
Shenfu decoction (SFD) can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF). We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF–MS)-based metabolomic study to increase the understanding of CHF and assess the efficacies and mechanisms of SFD in treating CHF induced by coronary artery ligation in rats. Based on unsupervised principal component analysis, there was a clear separation between the CHF and sham surgery group, which revealed that CHF disturbed the metabolism of endogenous substances and significantly altered the urine metabolite fingerprints. After SFD treatment, the metabolomics profile found in CHF was significantly reversed, shifting much closer to normal controls and sham surgery group, indicating that SFD has therapeutic effects in CHF, which is in accordance with the hemodynamic assay results. Metabolomic pathway analysis demonstrated that several pathways including fatty acid biosynthesis, fatty acid elongation, steroid biosynthesis, galactose metabolism, and amino acid metabolism were significantly altered in CHF rats. Therefore, we may infer that SFD shows therapeutic efficacy in CHF by restoring these disturbed metabolic pathways, especially those related to energy metabolism. This study offers new methodologies for increasing the understanding of CHF and systematically characterizing the efficacies and mechanisms of SFD in treating CHF. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model
Molecules 2015, 20(7), 11930-11940; doi:10.3390/molecules200711930
Received: 25 May 2015 / Revised: 19 June 2015 / Accepted: 24 June 2015 / Published: 30 June 2015
Cited by 3 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text
Abstract
We recently reported the protective effects of chlorogenic acid (CGA) in a transient middle cerebral artery occlusion (tMCAo) rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA) was selected for further study after
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We recently reported the protective effects of chlorogenic acid (CGA) in a transient middle cerebral artery occlusion (tMCAo) rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA) was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion) were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP)-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p.) dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB) leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Characterization of Different Sumac and Pomegranate Extracts Effective against Botrytis cinerea Rots
Molecules 2015, 20(7), 11941-11958; doi:10.3390/molecules200711941
Received: 7 May 2015 / Revised: 18 June 2015 / Accepted: 23 June 2015 / Published: 30 June 2015
Cited by 12 | PDF Full-text (882 KB) | HTML Full-text | XML Full-text
Abstract
Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were
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Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were applied and extracts were characterized through Ultra Fast High Performance Liquid Chromatography coupled to Photodiode array detector and Electrospray ionization Mass spectrometer (UPLC-PDA-ESI/MSn) for their phenol and anthocyanin contents. The concentrated pomegranate peel extract (PGE-C) was the richest in phenols (66.97 g gallic acid equivalents/kg) while the concentrated sumac extract from fruits (SUF-C) showed the highest anthocyanin amount (171.96 mg cyanidin 3-glucoside equivalents/kg). Both phenolic and anthocyanin profile of pomegranate and sumac extracts were quite different: pomegranate extract was rich in cyanidin 3-glucoside, pelargonidin 3-glucoside and ellagic acid derivatives, while sumac extract was characterized by 7-methyl-cyanidin 3-galactoside and gallic acid derivatives. The concentrated extracts from both pomegranate peel and sumac leaves significantly reduced the development of Botrytis rots. In particular, the extract from pomegranate peel completely inhibited the pathogen at different intervals of time (0, 12, and 24 h) between treatment and pathogen inoculation on fruits maintained at 22–24 °C and high relative humidity (RH). This extract may represent a valuable alternative to control postharvest fungal rots in view of its high efficacy because of the low cost of pomegranate peel, which is a waste product of processing factories. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Induction of Mitochondrial Dependent Apoptosis in Human Leukemia K562 Cells by Meconopsis integrifolia: A Species from Traditional Tibetan Medicine
Molecules 2015, 20(7), 11981-11993; doi:10.3390/molecules200711981
Received: 22 February 2015 / Revised: 15 May 2015 / Accepted: 18 May 2015 / Published: 30 June 2015
Cited by 3 | PDF Full-text (3743 KB) | HTML Full-text | XML Full-text
Abstract
Objectives: Meconopsis integrifolia (M. integrifolia) is one of the most popular members in Traditional Tibetan Medicine. This study aimed to investigate the anticancer effect of M. integrifolia and to detect the underlying mechanisms of these effects. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
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Objectives: Meconopsis integrifolia (M. integrifolia) is one of the most popular members in Traditional Tibetan Medicine. This study aimed to investigate the anticancer effect of M. integrifolia and to detect the underlying mechanisms of these effects. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and trypan blue assay were used to evaluate the cytotoxicity of M. integrifolia. Changes in cell nuclear morphology and reactive oxygen species (ROS) level were observed by fluorescent microscopy. Apoptosis ratio, DNA damage and mitochondrial membrane potential (MMP) loss were analyzed by flow cytometry. Western blotting assay was adopted to detect the proteins related to apoptosis. Immunofluorescence was used to observe the release of cytochrome C. Results: The obtained data revealed that M. integrifolia could significantly inhibit K562 cell viability, mainly by targeting apoptosis induction and cell cycle arrest in G2/M phase. Collapse in cell morphology, chromatin condensation, DNA damage and ROS accumulation were observed. Further mechanism detection revealed that mitochondrion might be a key factor in M. integrifolia-induced apoptosis. Conclusions: M. integrifolia could induce mitochondria mediated apoptosis and cell cycle arrest in G2/M phase with little damage to normal cells, suggesting that M. integrifolia might be a potential and efficient anticancer agent that deserves further investigation. Full article
Open AccessArticle Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines
Molecules 2015, 20(7), 11994-12015; doi:10.3390/molecules200711994
Received: 29 May 2015 / Revised: 21 June 2015 / Accepted: 25 June 2015 / Published: 30 June 2015
Cited by 5 | PDF Full-text (4867 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To examine the effect of hydrophobicity on the anticancer activity of 1,4-naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl- or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell
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To examine the effect of hydrophobicity on the anticancer activity of 1,4-naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl- or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell lines in vitro. The cytotoxicity of these derivatives was assayed against HT-29, SW480, HepG2, MCF-7 and HL-60 cells by the MTT assay. Among them, 2-hydroxy-3-farnesyl-1,4-naphthoquinone (11a) was found to be the most cytotoxic against these cell lines. Our results showed that the effectiveness of compound 11a may be attributed to its suppression of the survival of HT-29. Secondly, in the Hoechst 33258 staining test, compound 11a-treated cells exhibited nuclear condensation typical of apoptosis. Additionally, cell cycle analysis by flow cytometry indicated that compound 11a arrested HT-29 cells in the S phase. Furthermore, cell death detected by Annexin V-FITC/propidium iodide staining showed that compound 11a efficiently induced apoptosis of HT-29 in a concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent. Full article
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Open AccessArticle Studies on Chemical Composition, Antimicrobial and Antioxidant Activities of Five Thymus vulgaris L. Essential Oils
Molecules 2015, 20(7), 12016-12028; doi:10.3390/molecules200712016
Received: 8 May 2015 / Revised: 19 June 2015 / Accepted: 24 June 2015 / Published: 1 July 2015
Cited by 13 | PDF Full-text (794 KB) | HTML Full-text | XML Full-text
Abstract
This study is aimed at assessing the essential oil composition, total phenolic content, antimicrobial and antioxidant activities of Thymus vulgaris collected in five different area of the Campania Region, Southern Italy. The chemical composition of the essential oils was studied by GC-flame ionization
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This study is aimed at assessing the essential oil composition, total phenolic content, antimicrobial and antioxidant activities of Thymus vulgaris collected in five different area of the Campania Region, Southern Italy. The chemical composition of the essential oils was studied by GC-flame ionization detector (FID) and GC/MS; the biological activities were evaluated through determination of MIC and minimum bactericidal concentration (MBC) and evaluation of antioxidant activity. In total, 134 compounds were identified. The oils were mainly composed of phenolic compounds, and all oils belonged to the chemotype thymol. The antimicrobial activity of the five oils was assayed against ten bacterial strains. The oils showed different inhibitory activity against some Gram-positive pathogens. The total phenol content in the essential oils ranged from 77.6–165.1 mg gallic acid equivalents (GAE)/g. The results reported here may help to shed light on the complex chemotaxonomy of the genus Thymus. These oils could be used in many fields as natural preservatives of food and as nutraceuticals. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Novel 1-(4-Substituted pyridine-3-sulfonyl)-3-phenylureas with Potential Anticancer Activity
Molecules 2015, 20(7), 12029-12044; doi:10.3390/molecules200712029
Received: 2 April 2015 / Revised: 16 June 2015 / Accepted: 24 June 2015 / Published: 1 July 2015
Cited by 7 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 4-substituted-N-(phenylcarbamoyl)-3-pyridinesulfonamides 1127 have been synthesized by the reaction of 4-substituted pyridine-3-sulfonamides 210 with the appropriate aryl isocyanates in presence of potassium carbonate. The in vitro anticancer activity of compounds 11, 12,
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A series of novel 4-substituted-N-(phenylcarbamoyl)-3-pyridinesulfonamides 1127 have been synthesized by the reaction of 4-substituted pyridine-3-sulfonamides 210 with the appropriate aryl isocyanates in presence of potassium carbonate. The in vitro anticancer activity of compounds 11, 12, 1421 and 2426 was evaluated at the U.S. National Cancer Institute and in light of the results, some structure-activity relationships were discussed. The most prominent compound, N-[(4-chlorophenyl)carbamoyl]-4-[4-(3,4-dichlorophenyl)piperazin-1-yl]pyridine-3-sulfonamide (21) has exhibited a good activity profile and selectivity toward the subpanels of leukemia, colon cancer and melanoma, with average GI50 values ranging from 13.6 to 14.9 µM. Full article
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Open AccessArticle The Antioxidant Properties and Inhibitory Effects on HepG2 Cells of Chicory Cultivated Using Three Different Kinds of Fertilizers in the Absence and Presence of Pesticides
Molecules 2015, 20(7), 12061-12075; doi:10.3390/molecules200712061
Received: 5 June 2015 / Revised: 25 June 2015 / Accepted: 29 June 2015 / Published: 1 July 2015
PDF Full-text (791 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to explore the antioxidant levels and anticancer properties of chicory cultivated using three different kinds of fertilizers (i.e., developed, organic, and chemical) in the presence and absence of pesticides. Phenolic phytochemicals, including total polyphenols and
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The objective of this study was to explore the antioxidant levels and anticancer properties of chicory cultivated using three different kinds of fertilizers (i.e., developed, organic, and chemical) in the presence and absence of pesticides. Phenolic phytochemicals, including total polyphenols and flavonoids, and antioxidant activities, including reducing power, ABTS+ and DPPH radical scavenging activity, were analyzed using several antioxidant assays. HepG2 cell viability was analyzed using the MTT assay. The antioxidant properties of chicory were found to increase when cultivated with chemical fertilizer in the absence of pesticides. On the other hand, antioxidant capacity was higher in chicory cultivated with eco-developed fertilizer even in the presence of pesticides. Chicory grown using eco-developed or organic fertilizer was more effective in suppressing the proliferation of HepG2 cells when compared to chicory grown with chemical fertilizer. This effect was time dependent, regardless of treatment with or without pesticides. In conclusion, the antioxidant activity of chicory were affected by the presence or absence of pesticides. However, developed and organic fertilizers showed a strong anti-proliferative effect against HepG2 cells, regardless of the presence or absence of pesticides. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Development of Radiolabeled Membrane Type-1 Matrix Metalloproteinase Activatable Cell Penetrating Peptide Imaging Probes
Molecules 2015, 20(7), 12076-12092; doi:10.3390/molecules200712076
Received: 29 April 2015 / Revised: 7 June 2015 / Accepted: 29 June 2015 / Published: 2 July 2015
Cited by 2 | PDF Full-text (911 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevated MT1-MMP levels in adverse cardiac remodelling. Three ACPP analogs
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Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevated MT1-MMP levels in adverse cardiac remodelling. Three ACPP analogs were synthesized and the most potent ACPP analog was selected using MT1-MMP sensitivity and enzyme specificity assays. This ACPP, called ACPP-B, showed high sensitivity towards MT1-MMP, soluble MMP-2, and MT2-MMP, while limited sensitivity was measured for other members of the MMP family. In in vitro cell assays, radiolabeled ACPP-B showed efficient cellular uptake upon activation. A pilot in vivo study showed increased uptake of the radiolabeled probe in regions of infarcted myocardium compared to remote myocardium, warranting further in vivo evaluation. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
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Open AccessArticle Chemical Composition and Antioxidant and Antibacterial Activities of an Essential Oil Extracted from an Edible Seaweed, Laminaria japonica L.
Molecules 2015, 20(7), 12093-12113; doi:10.3390/molecules200712093
Received: 20 April 2015 / Revised: 23 June 2015 / Accepted: 25 June 2015 / Published: 2 July 2015
Cited by 9 | PDF Full-text (3914 KB) | HTML Full-text | XML Full-text
Abstract
Laminaria japonica L. is among the most commonly consumed seaweeds in northeast Asia. In the present study, L. japonica essential oil (LJEO) was extracted by microwave-hydrodistillation and analyzed by gas chromatography and mass spectroscopy. LJEO contained 21 volatile compounds, comprising 99.76% of the
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Laminaria japonica L. is among the most commonly consumed seaweeds in northeast Asia. In the present study, L. japonica essential oil (LJEO) was extracted by microwave-hydrodistillation and analyzed by gas chromatography and mass spectroscopy. LJEO contained 21 volatile compounds, comprising 99.76% of the total volume of the essential oil, primarily tetradeconoic acid (51.75%), hexadecanoic acid (16.57%), (9Z,12Z)-9,12-Octadecadienoic acid (12.09%), and (9Z)-hexadec-9-enoic acid (9.25%). Evaluation of the antibacterial potential against three foodborne pathogens, Bacillus cereus ATCC 10876, Escherichia coli O157:H7 ATCC 43890, and Staphylococcus aureus ATCC 49444, revealed that LJEO at a concentration of 25 mg/paper disc exerted high antibacterial activity against S. aureus (11.5 ± 0.58 mm inhibition zone) and B. cereus (10.5 ± 0.57 mm inhibition zone), but no inhibition of E. coli O157:H7. LJEO also displayed DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity (80.45%), superoxide anion scavenging activity (54.03%), and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical and hydroxyl radical scavenging at 500 µg/mL. Finally, LJEO showed high inhibition of lipid peroxidation with strong reducing power. In conclusion, LJEO from edible seaweed is an inexpensive but favorable resource with strong antibacterial capacity as well as free radical scavenging and antioxidant activity; therefore, it has the potential for use in the food, cosmetics, and pharmaceutical industries. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Quantitative 1H-NMR Method for the Determination of Tadalafil in Bulk Drugs and its Tablets
Molecules 2015, 20(7), 12114-12124; doi:10.3390/molecules200712114
Received: 5 June 2015 / Revised: 21 June 2015 / Accepted: 25 June 2015 / Published: 2 July 2015
Cited by 6 | PDF Full-text (992 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple, rapid, accurate, and selective quantitative nuclear magnetic resonance method for the determination of tadalafil in bulk drugs and its tablets was established and evaluated. Spectra were obtained in dimethylsulfoxide-d6 using 2,4-dinitrotoluene as the internal standard. In this study, the
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A simple, rapid, accurate, and selective quantitative nuclear magnetic resonance method for the determination of tadalafil in bulk drugs and its tablets was established and evaluated. Spectra were obtained in dimethylsulfoxide-d6 using 2,4-dinitrotoluene as the internal standard. In this study, the method’s linearity, range, limit of quantification, stability, precision, and accuracy were validated. The results were consistent with those obtained from high-performance liquid chromatography analysis. Thus, the proposed method is a useful and practical tool for the determination of tadalafil in bulk drugs and its tablets. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Post-Synthetic Shaping of Porosity and Crystal Structure of Ln-Bipy-MOFs by Thermal Treatment
Molecules 2015, 20(7), 12125-12153; doi:10.3390/molecules200712125
Received: 17 April 2015 / Accepted: 23 June 2015 / Published: 3 July 2015
Cited by 4 | PDF Full-text (3429 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reaction of anhydrous lanthanide chlorides together with 4,4′-bipyridine yields the MOFs 2[Ln2Cl6(bipy)3]·2bipy, with Ln = Pr − Yb, bipy = 4,4′-bipyridine, and 3[La2Cl6(bipy)5]·4bipy. Post-synthetic thermal treatment
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The reaction of anhydrous lanthanide chlorides together with 4,4′-bipyridine yields the MOFs 2[Ln2Cl6(bipy)3]·2bipy, with Ln = Pr − Yb, bipy = 4,4′-bipyridine, and 3[La2Cl6(bipy)5]·4bipy. Post-synthetic thermal treatment in combination with different vacuum conditions was successfully used to shape the porosity of the MOFs. In addition to the MOFs microporosity, a tuneable mesoporosity can be implemented depending on the treatment conditions as a surface morphological modification. Furthermore, thermal treatment without vacuum results in several identifiable crystalline high-temperature phases. Instead of collapse of the frameworks upon heating, further aggregation under release of bipy is observed. 3[LaCl3(bipy)] and 2[Ln3Cl9(bipy)3], with Ln = La, Pr, Sm, and 1[Ho2Cl6(bipy)2] were identified and characterized, which can also exhibit luminescence. Besides being released upon heating, the linker 4,4′-bipyridine can undergo activation of C-C bonding in ortho-position leading to the in-situ formation of 4,4′:2′,2′′:4′′,4′′′-quaterpyridine (qtpy). qtpy can thereby function as linker itself, as shown for the formation of the network 2[Gd2Cl6(qtpy)2(bipy)2]·bipy. Altogether, the manuscript elaborates the influence of thermal treatment beyond the usual activation procedures reported for MOFs. Full article
(This article belongs to the Special Issue Metal-Organic Frameworks: Chemistry and Applications)
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Open AccessArticle Antioxidative and Anticanceric Activities of Magnolia (Magnolia denudata) Flower Petal Extract Fermented by Pediococcus acidilactici KCCM 11614
Molecules 2015, 20(7), 12154-12165; doi:10.3390/molecules200712154
Received: 14 May 2015 / Revised: 29 June 2015 / Accepted: 30 June 2015 / Published: 3 July 2015
Cited by 5 | PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the effects of magnolia (Magnolia (M.) denudata) extract fermentation in increasing the extract’s antioxidative and anticancer activities were investigated. Magnolia was fermented by Pediococcus acidilactici KCCM 11614. The total phenolic content was determined by the Folin-Ciocalteu’s
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In this study, the effects of magnolia (Magnolia (M.) denudata) extract fermentation in increasing the extract’s antioxidative and anticancer activities were investigated. Magnolia was fermented by Pediococcus acidilactici KCCM 11614. The total phenolic content was determined by the Folin-Ciocalteu’s method and the antioxidative effects by 1,1-diphenyl-2-picrylhydrazy (DPPH) and ferric reducing ability of plasma (FRAP) assay. Anticancer activity against cancer and normal cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Total phenolic content during fermentation increased from 38.1 to 47.0 mg gallic acid equivalent (GAE)/g of solid matter. The radical scavenging activity was 91.4% after 72 h fermentation. Fermented magnolia’s antioxidative effect was threefold higher than that of the (non-fermented) control. Fermentation (48 h) increased anticanceric activity against AGS, LoVo, and MCF-7 cancer cells 1.29- to 1.36-fold compared with that of the control, but did not affect MRC-5 (normal) cells, suggesting that fermented magnolia could be used as a natural antioxidative and anticancer agent. Full article
Open AccessArticle Biofunctional Constituents from Michelia compressa var. lanyuensis with Anti-Melanogenic Properties
Molecules 2015, 20(7), 12166-12174; doi:10.3390/molecules200712166
Received: 29 May 2015 / Revised: 26 June 2015 / Accepted: 1 July 2015 / Published: 3 July 2015
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Abstract
Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (−)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (−)-bornesitol and β-sitostenone. These compounds were screened for anti-proliferation and anti-tyrosinase activities in B16F10 cells.
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Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (−)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (−)-bornesitol and β-sitostenone. These compounds were screened for anti-proliferation and anti-tyrosinase activities in B16F10 cells. Liriodenine, pressalanine A, (−)-bornesitol and β-sitostenone displayed cytotoxicity at high concentration (100 μM), but liriodenine (5 μM), (−)-N-acetylanonaine (10 μM), and β-sitostenone (5 μM) inhibit tyrosinase activity and reduce the melanin content in B16F10 cells without cytotoxicity, suggesting that liriodenine and β-sitostenone could be safe and potentially used in cosmetic skin whitening. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Novel Fluorinated Phosphorus–Sulfur Heteroatom Compounds: Synthesis and Characterization of Ferrocenyl- and Aryl-Phosphonofluorodithioic Salts, Adducts, and Esters
Molecules 2015, 20(7), 12175-12197; doi:10.3390/molecules200712175
Received: 7 June 2015 / Revised: 27 June 2015 / Accepted: 30 June 2015 / Published: 3 July 2015
Cited by 3 | PDF Full-text (2545 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel ferrocenyl- and aryl-phosphonofluorodithioic salts, adducts, and esters has been prepared. The reaction of 2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide {[FcP(μ-S)S]2, FcLR} with dry KF or tetrabutylammonium fluoride (TBAF) led to the corresponding potassium and tetrabutylammonium salts of ferrocenyldithiofluorophosphinic acids. Treating
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A series of novel ferrocenyl- and aryl-phosphonofluorodithioic salts, adducts, and esters has been prepared. The reaction of 2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide {[FcP(μ-S)S]2, FcLR} with dry KF or tetrabutylammonium fluoride (TBAF) led to the corresponding potassium and tetrabutylammonium salts of ferrocenyldithiofluorophosphinic acids. Treating potassium ferrocenyldithiofluorophosphinic acid with an equimolar amount of tetraphenylphosphonium chloride readily yielded the corresponding organic adducts, and with mono- and di-halogenated alkanes generated a series of the corresponding esters of ferrocenylphosphonofluoridodithioates. Similarly, using 1,3-epithionaphtho[1,8-cd][1,2,6] oxadiphosphinine 1,3-disulfide or Belleau’s Reagent in place of FcLR resulted in the corresponding novel salts, adducts, and ester derivatives. All new compounds have been characterized by means of multi-NMR (1H, 13C, 31P, 19F) spectroscopy and accurate mass measurement in conjunction with single crystal X-ray crystallography of four structures. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessCommunication Enzyme Inhibitory Radicinol Derivative from Endophytic fungus Bipolaris sorokiniana LK12, Associated with Rhazya stricta
Molecules 2015, 20(7), 12198-12208; doi:10.3390/molecules200712198
Received: 3 May 2015 / Revised: 17 June 2015 / Accepted: 30 June 2015 / Published: 3 July 2015
Cited by 5 | PDF Full-text (920 KB) | HTML Full-text | XML Full-text
Abstract
Endophytes, living inside plant tissues, play an essential role in plant growth and development, whilst producing unique bioactive secondary metabolites. In the current study, the endophytic fungus Bipolaris sorokiniana LK12 was isolated from the leaves of ethno-medicinal and alkaloidal rich Rhazya stricta. The
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Endophytes, living inside plant tissues, play an essential role in plant growth and development, whilst producing unique bioactive secondary metabolites. In the current study, the endophytic fungus Bipolaris sorokiniana LK12 was isolated from the leaves of ethno-medicinal and alkaloidal rich Rhazya stricta. The bulk amount of ethyl acetate extract of fungus was subjected to advance column chromatographic techniques, which resulted in the isolation of a new radicinol derivative, bipolarisenol (1). It was found to be a derivative of radicinol. The structure elucidation was carried out by the combined use of 1D and 2D nuclear magnetic resonance, infrared spectroscopy, mass, and UV spectrometric analyses. The bipolarisenol was assessed for its potential role in enzyme inhibition of urease and acetyl cholinesterase (AChE). Results showed that bipolarisenol significantly inhibited the AChE activity with low IC50 (67.23 ± 5.12 µg·mL−1). Bipolarisenol inhibited urease in a dose-dependent manner with high IC50 (81.62 ± 4.61 µg·mL−1). The new compound also showed a moderate anti-lipid peroxidation potential (IC50 = 168.91 ± 4.23 µg·mL−1). In conclusion, endophytes isolated from medicinal plants possess a unique potential to be considered for future drug discovery. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Qualitative and Quantitative Analysis of Phenolic Acids, Flavonoids and Iridoid Glycosides in Yinhua Kanggan Tablet by UPLC-QqQ-MS/MS
Molecules 2015, 20(7), 12209-12228; doi:10.3390/molecules200712209
Received: 6 April 2015 / Revised: 17 June 2015 / Accepted: 19 June 2015 / Published: 3 July 2015
Cited by 4 | PDF Full-text (2681 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple, rapid and specific ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed for the analysis of 29 bioactive components (10 phenolic acids, 16 flavonoids, and three iridoid glycosides) in Yinhua Kanggan tablet (YHKGT), a herbal prescription used for treating upper respiratory
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A simple, rapid and specific ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed for the analysis of 29 bioactive components (10 phenolic acids, 16 flavonoids, and three iridoid glycosides) in Yinhua Kanggan tablet (YHKGT), a herbal prescription used for treating upper respiratory infections, fevers, coughs and pharyngalgia. The separation was successfully achieved using a Waters Cortecs UPLC C18 column (50 × 2.1 mm, 1.6 μm) and gradient elution with water-0.1% formic acid and acetonitrile. Polarity switching mode was used in the optimization of multiple reaction monitoring conditions. The analytical method was validated for linearity, precision and accuracy. Calibration curves for the 29 marker compounds showed good linear regression (r > 0.9982). The limits of detection (LOD) and limits of quantification (LOQ) for the 29 analytes were in the range of 0.03–4.99 ng/mL and 0.16–14.87 ng/mL, respectively. The relative standard deviation (RSD) values of intra-day precision, inter-day precision, repeatability, and stability were less than 2.79%, 4.87%, 4.18% and 4.71%, respectively. The recoveries of the 29 marker compounds were in the range of 94.67%–104.78% (RSD ≤ 4.72%). These results have shown that this developed method was efficient for the quality evaluation of YHKGT. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Protective Effect of Procyanidin B2 against CCl4-Induced Acute Liver Injury in Mice
Molecules 2015, 20(7), 12250-12265; doi:10.3390/molecules200712250
Received: 20 April 2015 / Revised: 24 June 2015 / Accepted: 24 June 2015 / Published: 3 July 2015
Cited by 14 | PDF Full-text (2958 KB) | HTML Full-text | XML Full-text
Abstract
Procyanidin B2 has demonstrated several health benefits and medical properties. However, its protective effects against CCl4-induced hepatotoxicity have not been clarified. The present study aimed to investigate the hepatoprotective effects of procyanidin B2 in CCl4-treated mice. Our data showed
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Procyanidin B2 has demonstrated several health benefits and medical properties. However, its protective effects against CCl4-induced hepatotoxicity have not been clarified. The present study aimed to investigate the hepatoprotective effects of procyanidin B2 in CCl4-treated mice. Our data showed that procyanidin B2 significantly decreased the CCl4-induced elevation of serum alanine aminotransferase activities, as well as improved hepatic histopathological abnormalities. Procyanidin B2 also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD, CAT and GSH-Px. Further research demonstrated that procyanidin B2 decreased the expression of TNF-α, IL-1β, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as inhibited the translocation of nuclear factor-kappa B (NF-κB) p65 from the cytosol to the nuclear fraction in mouse liver. Moreover, CCl4-induced apoptosis in mouse liver was measured by (terminal-deoxynucleotidyl transferase mediated nick end labeling) TUNEL assay and the cleaved caspase-3. Meanwhile, the expression of apoptosis-related proteins Bax and Bcl-xL was analyzed by Western blot. Results showed that procyanidin B2 significantly inhibited CCl4-induced hepatocyte apoptosis, markedly suppressed the upregulation of Bax expression and restored the downregulation of Bcl-xL expression. Overall, the findings indicated that procyanidin B2 exhibited a protective effect on CCl4-induced hepatic injury by elevating the antioxidative defense potential and consequently suppressing the inflammatory response and apoptosis of liver tissues. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Evaluation of New Podophyllotoxin Derivatives with in Vitro Anticancer Activity
Molecules 2015, 20(7), 12266-12279; doi:10.3390/molecules200712266
Received: 28 April 2015 / Revised: 28 June 2015 / Accepted: 29 June 2015 / Published: 6 July 2015
Cited by 1 | PDF Full-text (782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel podophyllotoxin derivatives were designed and synthesized. The cytotoxic activities of these compounds were tested against three tumor cell lines (HeLa, K562, and K562/A02). Most of the derivatives (IC50 = 1–20 μM) were found to have stronger cell growth
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A series of novel podophyllotoxin derivatives were designed and synthesized. The cytotoxic activities of these compounds were tested against three tumor cell lines (HeLa, K562, and K562/A02). Most of the derivatives (IC50 = 1–20 μM) were found to have stronger cell growth inhibitory activity than positive control etoposide. Among them, 4β-N-[(E)-(5-((4-(4-nitrophenyl)-piperazin-1-yl)methyl)furan-2-yl)prop-2-en-1-amine]-4-desoxy-podophyllotoxin (9l) demonstrated significant inhibitory activity against HeLa, K562, and K562/A02 cell lines with IC50 values of 7.93, 6.42, 6.89 μM, respectively. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Quantification of Polyfunctional Thiols in Wine by HS-SPME-GC-MS Following Extractive Alkylation
Molecules 2015, 20(7), 12280-12299; doi:10.3390/molecules200712280
Received: 30 May 2015 / Revised: 29 June 2015 / Accepted: 30 June 2015 / Published: 6 July 2015
Cited by 3 | PDF Full-text (2270 KB) | HTML Full-text | XML Full-text
Abstract
Analyses of key odorous polyfunctional volatile thiols in wines (3-mercaptohexanol (3-MH), 3-mercaptohexylacetate (3-MHA), and 4-mercapto-4-methyl-2-pentanone (4-MMP)) are challenging due to their high reactivity and ultra-trace concentrations, especially when using conventional gas-chromatography electron impact mass spectrometry (GC-EI-MS). We describe a method in which thiols
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Analyses of key odorous polyfunctional volatile thiols in wines (3-mercaptohexanol (3-MH), 3-mercaptohexylacetate (3-MHA), and 4-mercapto-4-methyl-2-pentanone (4-MMP)) are challenging due to their high reactivity and ultra-trace concentrations, especially when using conventional gas-chromatography electron impact mass spectrometry (GC-EI-MS). We describe a method in which thiols are converted to pentafluorobenzyl (PFB) derivatives by extractive alkylation and the organic layer is evaporated prior to headspace solid phase microextraction (HS-SPME) and GC-EI-MS analysis. Optimal parameters were determined by response surface area modeling. The addition of NaCl solution to the dried SPME vials prior to extraction resulted in up to less than fivefold improvement in detection limits. Using 40 mL wine samples, limits of detection for 4-MMP, 3-MH, and 3-MHA were 0.9 ng/L, 1 ng/L, and 17 ng/L, respectively. Good recovery (90%–109%) and precision (5%–11% RSD) were achieved in wine matrices. The new method was used to survey polyfunctional thiol concentrations in 61 commercial California and New York State wines produced from V. vinifera (Riesling, Gewürztraminer, Cabernet Sauvignon, Sauvignon blanc and non-varietal rosé wines), V. labruscana (Niagara), and Vitis spp. (Cayuga White). Mean 4-MMP concentrations in New York Niagara (17 ng/L) were not significantly different from concentrations in Sauvignon blanc, but were significantly higher than 4-MMP in other varietal wines. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives
Molecules 2015, 20(7), 12300-12313; doi:10.3390/molecules200712300
Received: 2 June 2015 / Revised: 1 July 2015 / Accepted: 2 July 2015 / Published: 6 July 2015
PDF Full-text (842 KB) | HTML Full-text | XML Full-text
Abstract
This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine) by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The
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This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine) by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The obtained Mannich bases were acylated to their corresponding N-acetyl derivatives. All compounds were characterized by 1H-NMR, 13C-NMR and MS spectrometry. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Calophyllolide Content in Calophyllum inophyllum at Different Stages of Maturity and Its Osteogenic Activity
Molecules 2015, 20(7), 12314-12327; doi:10.3390/molecules200712314
Received: 17 April 2015 / Revised: 26 June 2015 / Accepted: 1 July 2015 / Published: 7 July 2015
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Abstract
Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated
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Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated using silica gel and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The fruits were harvested from September to December in 2011; a quantitative analysis of the calophyllolide content was conducted using HPLC to explore the differences between the different parts of the fruit during the growing season. The results showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts, and dried nuts contain approximately 2 mg·g1 of calophyllolide. The calophyllolide levels in the nuts decreased during maturity. In addition, calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced by increasing mineralization and ALP staining. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Study on the Spectrophotometric Detection of Free Fatty Acids in Palm Oil Utilizing Enzymatic Reactions
Molecules 2015, 20(7), 12328-12340; doi:10.3390/molecules200712328
Received: 10 April 2015 / Revised: 29 May 2015 / Accepted: 1 June 2015 / Published: 7 July 2015
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Abstract
In this paper, a comprehensive study has been made on the detection of free fatty acids (FFAs) in palm oil via an optical technique based on enzymatic aminolysis reactions. FFAs in crude palm oil (CPO) were converted into fatty hydroxamic acids (FHAs) in
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In this paper, a comprehensive study has been made on the detection of free fatty acids (FFAs) in palm oil via an optical technique based on enzymatic aminolysis reactions. FFAs in crude palm oil (CPO) were converted into fatty hydroxamic acids (FHAs) in a biphasic lipid/aqueous medium in the presence of immobilized lipase. The colored compound formed after complexation between FHA and vanadium (V) ion solution was proportional to the FFA content in the CPO samples and was analyzed using a spectrophotometric method. In order to develop a rapid detection system, the parameters involved in the aminolysis process were studied. The utilization of immobilized lipase as catalyst during the aminolysis process offers simplicity in the product isolation and the possibility of conducting the process under extreme reaction conditions. A good agreement was found between the developed method using immobilized Thermomyces lanuginose lipase as catalyst for the aminolysis process and the Malaysian Palm Oil Board (MPOB) standard titration method (R2 = 0.9453). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Multidimensional Transition Metal Complexes Based on 3-Amino-1H-1,2,4-triazole-5-carboxylic Acid: From Discrete Mononuclear Complexes to Layered Materials
Molecules 2015, 20(7), 12341-12363; doi:10.3390/molecules200712341
Received: 1 June 2015 / Revised: 22 June 2015 / Accepted: 25 June 2015 / Published: 7 July 2015
Cited by 1 | PDF Full-text (8064 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and structural characterization of five transition metal complexes with different dimensionality and incorporating residues of 3-amino-1H-1,2,4-triazole-5-carboxylic acid (H2atrc) is reported: [Zn(Hatrc)2(H2O)] (1), [Mn(Hatrc)2(H2O)2]·2H2O
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The synthesis and structural characterization of five transition metal complexes with different dimensionality and incorporating residues of 3-amino-1H-1,2,4-triazole-5-carboxylic acid (H2atrc) is reported: [Zn(Hatrc)2(H2O)] (1), [Mn(Hatrc)2(H2O)2]·2H2O (2), [Fe2(Hatrc)4(OH)2]·6H2O (3), [Cd(Hatrc)2(H2O)]n (4), and [Mn(atrc)(H2O)]n·nH2O (5). These materials could be prepared from solution (13), diffusion (4), or hydrothermal reactions (5) with various anions and L:M ratios. Structural details were revealed by single crystal X-ray diffraction. The discrete units composing compounds 13, the polymeric 1D chain of 4 and the 2D layer of 5 are further extended into 3D supramolecular architectures through the formation of hydrogen bonds. Full article
(This article belongs to the Special Issue Metal-Organic Frameworks: Chemistry and Applications)
Open AccessArticle Mimicking the Lipid Peroxidation Inhibitory Activity of Phospholipid Hydroperoxide Glutathione Peroxidase (GPx4) by Using Fatty Acid Conjugates of a Water-Soluble Selenolane
Molecules 2015, 20(7), 12364-12375; doi:10.3390/molecules200712364
Received: 12 May 2015 / Revised: 16 June 2015 / Accepted: 1 July 2015 / Published: 7 July 2015
Cited by 3 | PDF Full-text (783 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of fatty acid conjugates of trans-3,4-dihydroxy-1-selenolane (DHS) were synthesized by reacting DHS with appropriate acid chlorides. The obtained monoesters were evaluated for their antioxidant capacities by the lipid peroxidation assay using a lecithin/cholesterol liposome as a model system. The observed
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A series of fatty acid conjugates of trans-3,4-dihydroxy-1-selenolane (DHS) were synthesized by reacting DHS with appropriate acid chlorides. The obtained monoesters were evaluated for their antioxidant capacities by the lipid peroxidation assay using a lecithin/cholesterol liposome as a model system. The observed antioxidant capacities against accumulation of the lipid hydroperoxide (LOOH) increased with increasing the alkyl chain length and became saturated for dodecanoic acid (C12) or higher fatty acid monoesters, for which the capacities were much greater than those of DHS, its tridecanoic acid (C13) diester, and PhSeSePh. On the other hand, the bacteriostatic activity of myristic acid (C14) monoester, evaluated through the colony formation assay using Bacillus subtilis, indicated that it has higher affinity to bacterial cell membranes than parent DHS. Since DHS-fatty acid conjugates would inhibit lipid peroxidation through glutathione peroxidase (GPx)-like 2e mechanism, higher fatty acid monoesters of DHS can mimic the function of GPx4, which interacts with LOOH to reduce it to harmless alcohol (LOH). Importance of the balance between hydrophilicity and lipophilicity for the design of effective GPx4 mimics was suggested. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Molecular Clusters Size of Puerariae thomsonii Radix Aqueous Decoction and Relevance to Oral Absorption
Molecules 2015, 20(7), 12376-12388; doi:10.3390/molecules200712376
Received: 18 April 2015 / Revised: 4 June 2015 / Accepted: 23 June 2015 / Published: 7 July 2015
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Abstract
The multi-component system of traditional Chinese medicine (TCM) is very complicated. The clusters are dynamic aggregates whose molecules are held together by hydrogen-bonded, Van der Waals forces or the opposite charges of particles attract each other. In this paper, field emission scanning electron
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The multi-component system of traditional Chinese medicine (TCM) is very complicated. The clusters are dynamic aggregates whose molecules are held together by hydrogen-bonded, Van der Waals forces or the opposite charges of particles attract each other. In this paper, field emission scanning electron microscopy proved that molecules form clusters in Pueraria thomsonii Benth (Fenge) water decoction. Four kinds of Fenge water decoction, 0.07 g∙mL−1 (F-1), 0.1 g∙mL−1 (F-2), 0.17 g∙mL−1 (F-3), 0.35 g∙mL−1 (F-4); F-1, average diameter of molecular was about 120 nm; F-2, 195 nm; F-3, 256 nm; and F-4, 480 nm. The molecular size was shown to depend on concentration. Rabbits were given equal does of 2.8 g∙kg−1, to perfuse F-1, F-2, F-3, F-4 in volume of 80 mL, 56 mL, 33 mL, 17 mL, respectively. At 0–180 min to collect 2 mL blood from the rabbit ears middle arteries for metabolism fingerprints, the results show the particle size of molecular is smaller, the absorption of drugs is better instead. The acute blood stasis model rats were treatment with Fenge decoction of 1.5 g∙kg−1 for 14 days, the concentrations of Ang II in plasma were significantly lower in F-1 and F-2 groups than those in model group (p < 0.01 or p < 0.05), but there were no significantly difference in F-3 and F-4 groups than those in model group (p > 0.05). Despite the molecular aggregation is a common physical phenomenon, it influence on the kind and amount of molecule per unit volume. Molecules morphology influence on the absorption behavior of drugs in vivo therefore is to have an impact on pharmacological function. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle The Influence of the Terminal Phosphorothioate Diester Bond on the DNA Oxidation Process. An Experimental and Theoretical Approach
Molecules 2015, 20(7), 12400-12411; doi:10.3390/molecules200712400
Received: 6 March 2015 / Revised: 12 June 2015 / Accepted: 24 June 2015 / Published: 8 July 2015
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Abstract
In this study, the influence of the terminal phosphorothioate (PT) internucleotide bond in ds-DNA on the oxidation process was taken into consideration. The interaction of UV with the targeted oligonucleotide leads to an electron ejection and radical cation “hole” migration through the
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In this study, the influence of the terminal phosphorothioate (PT) internucleotide bond in ds-DNA on the oxidation process was taken into consideration. The interaction of UV with the targeted oligonucleotide leads to an electron ejection and radical cation “hole” migration through the ds-DNA until it is trapped irreversibly in a suitable place. Phosphorothiate internucleotide bonds were detected in the bacterial genome; however, their role is still unclear. In this study a PAGE analysis of irradiated ds-DNA showed that the degradation rea ction was slowed down by the presence PT next to the anthraquinone moiety. Further, theoretical study shows that [RP] AQ-PS-dG can adopt a slightly lower ionisation potential energy and triplet excited state with a subsequent slightly higher adiabatic electron affinity value in comparison with [SP] AQ-PS-dG and AQ-PO-dG. Moreover, the energy gap between HOMO and LUMO, indicated the radical stabilisation properties of [RP] AQ-PS-dG, which can hinder the charge transfer through ds-DNA. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Synthetic Development of New 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanines under Microwave Irradiation and Their Effects on Tumor Cell Lines and against Protein Kinases
Molecules 2015, 20(7), 12412-12435; doi:10.3390/molecules200712412
Received: 27 May 2015 / Revised: 17 June 2015 / Accepted: 30 June 2015 / Published: 8 July 2015
Cited by 4 | PDF Full-text (847 KB) | HTML Full-text | XML Full-text
Abstract
A new route to 3-(4-arylmethylamino)butyl-5-arylidene-2-thioxo-1,3-thiazolidine-4-one 9 was developed in six steps from commercial 1,4-diaminobutane 1 as starting material. The key step of this multi-step synthesis involved a solution phase “one-pot two-steps” approach assisted by microwave dielectric from N-(arylmethyl)butane-1,4-diamine hydrochloride 6af
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A new route to 3-(4-arylmethylamino)butyl-5-arylidene-2-thioxo-1,3-thiazolidine-4-one 9 was developed in six steps from commercial 1,4-diaminobutane 1 as starting material. The key step of this multi-step synthesis involved a solution phase “one-pot two-steps” approach assisted by microwave dielectric from N-(arylmethyl)butane-1,4-diamine hydrochloride 6af (as source of the first point diversity) and commercial bis-(carboxymethyl)-trithiocarbonate reagent 7 for construction of the rhodanine platform. This platform was immediately functionalized by Knoevenagel condensation under microwave irradiation with a series of aromatic aldehydes 3 as second point of diversity. These new compounds were prepared in moderate to good yields and the fourteen synthetic products 9an have been obtained with a Z-geometry about their exocyclic double bond. These new 5-arylidene rhodanines derivatives 9an were tested for their kinase inhibitory potencies against four protein kinases: Human cyclin-dependent kinase 5-p25, HsCDK5-p25; porcine Glycogen Synthase Kinase-3, GSK-3α/β; porcine Casein Kinase 1, SsCK1 and human HsHaspin. They have also been evaluated for their in vitro inhibition of cell proliferation (HuH7 D12, Caco 2, MDA-MB 231, HCT 116, PC3, NCI-H727, HaCat and fibroblasts). Among of all these compounds, 9j presented selective micromolar inhibition activity on SsCK1 and 9i exhibited antitumor activities in the HuH7 D12, MDA-MBD231 cell lines. Full article
(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)
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Open AccessArticle In Vitro Studies of Chromone-Tetrazoles against Pathogenic Protozoa, Bacteria, and Fungi
Molecules 2015, 20(7), 12436-12449; doi:10.3390/molecules200712436
Received: 29 May 2015 / Revised: 25 June 2015 / Accepted: 26 June 2015 / Published: 8 July 2015
Cited by 4 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In vitro studies to fourteen previously synthesized chromone-tetrazoles and four novel fluorine-containing analogs were conducted against pathogenic protozoan (Entamoeba histolytica), pathogenic bacteria (Pseudomonas aeruginosa, and Staphylococcus aureus), and human fungal pathogens (Sporothrix schenckii, Candida albicans,
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In vitro studies to fourteen previously synthesized chromone-tetrazoles and four novel fluorine-containing analogs were conducted against pathogenic protozoan (Entamoeba histolytica), pathogenic bacteria (Pseudomonas aeruginosa, and Staphylococcus aureus), and human fungal pathogens (Sporothrix schenckii, Candida albicans, and Candida tropicalis), which have become in a serious health problem, mainly in tropical countries. Full article
(This article belongs to the Special Issue Antiparasitic Agents)
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Open AccessArticle Potential Mechanism of Action of 3′-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus
Molecules 2015, 20(7), 12450-12458; doi:10.3390/molecules200712450
Received: 18 March 2015 / Revised: 1 July 2015 / Accepted: 2 July 2015 / Published: 8 July 2015
Cited by 1 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents
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Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3′-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3′-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3′-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents. Full article
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Open AccessArticle Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals
Molecules 2015, 20(7), 12459-12468; doi:10.3390/molecules200712459
Received: 29 May 2015 / Revised: 2 July 2015 / Accepted: 3 July 2015 / Published: 8 July 2015
Cited by 7 | PDF Full-text (552 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an
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Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds. Full article
Open AccessArticle Development and Characterization of Novel EST-SSRs from Larix gmelinii and Their Cross-Species Transferability
Molecules 2015, 20(7), 12469-12480; doi:10.3390/molecules200712469
Received: 27 March 2015 / Revised: 12 June 2015 / Accepted: 29 June 2015 / Published: 9 July 2015
Cited by 3 | PDF Full-text (1458 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A set of 899 L. gmelinii expression sequence tags (ESTs), available at the National Center of Biotechnology Information (NCBI), was employed to address the feasibility on development of simple sequence repeat (SSR) markers for Larch species. Totally, 634 non-redundant unigenes including 145 contigs
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A set of 899 L. gmelinii expression sequence tags (ESTs), available at the National Center of Biotechnology Information (NCBI), was employed to address the feasibility on development of simple sequence repeat (SSR) markers for Larch species. Totally, 634 non-redundant unigenes including 145 contigs and 489 singletons were finally identified and mainly involved in biosynthetic, metabolic processes and response to stress according to BLASTX results, gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) maps. Approximately 11.7% (74) unigenes contained 90 candidate SSRs, which were mainly trinucleotides (29, 32.2%) and dinucleotides (26, 28.9%). A relatively high frequency of SSRs was respectively found in the Open Reading Frame (ORF, about 54.4%) and 5′-untranslated region (5′-UTR, 31.2%), while a low frequency was observed in the 3′-untranslated region (3′-UTR, about 14.4%). Of the 45 novel EST-SSRs markers, nine were found to be polymorphic at two L. gmelinii populations. The number of alleles per locus (Na) ranged from two to four, and the observed (Ho) and expected (He) heterozygosity values were 0.200–0.733 and 0.408–0.604, respectively. The inbreeding coefficients (FIS) for all loci were more than zero except Lg41. Most of these 9EST-SSR markers were transferable to its related species L. kaempferi, L. principis-rupprechtii and L. olgensis. These novel EST-SSRs will be useful for further research on comparative genomics, genetic resources conservation and molecular breeding in larch trees. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Nitric Oxide-Releasing Aspirin Suppresses NF-κB Signaling in Estrogen Receptor Negative Breast Cancer Cells in Vitro and in Vivo
Molecules 2015, 20(7), 12481-12499; doi:10.3390/molecules200712481
Received: 9 April 2015 / Revised: 11 June 2015 / Accepted: 6 July 2015 / Published: 9 July 2015
Cited by 3 | PDF Full-text (2365 KB) | HTML Full-text | XML Full-text
Abstract
Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA)
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Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model using MDA-MB-231 cells. p-NO-ASA inhibited the growth of MDA-MB-231 and SK-BR-3 cells at 24 h, the respective IC50s were 13 ± 2 and 17 ± 2 μM; ASA had an IC50 of >3000 μM in both cell lines. The IC50s for m-NO-ASA in MDA-MB-231 and SK-BR-3 were 173 ± 15 and 185 ± 12 μM, respectively, therefore, implying p-NO-ASA as a stronger inhibitor of growth p-NO-ASA reduced cell growth by inhibiting proliferation, inducing apoptosis and causing G0/G1 cell cycle block. Activation of NF-κB was inhibited by both isomers as demonstrated by decreases in NF-κB-DNA binding and luciferase activity at 24 h, However, m-NO-ASA produced transient effects at 3 h such as increased NF-κB-DNA-binding, increased levels of nuclear p50, even though both isomers inhibited IκB degradation. Increase in nuclear p50 by m-NO-ASA was associated with translocation of p50 in to the nucleus as observed by immunoflouresence at 3 h. NO-ASA induced reactive oxygen species (ROS) as evidenced by overall increases in both H2DCFDA (2′,7′-dichlorodihydrofluorescein) and DHE (dihydroethidium)-derived fluorescence. Inhibition of ROS by N-acetyl-cysteine reversed the m-NO-ASA-mediated translocation of p50 in to the nucleus. In xenografts, p-NO-ASA inhibited tumor growth by inhibiting proliferation (PCNA and tumor volume), inducing apoptosis (TUNEL positive cells) and reducing NF-κB expression. Both isomers inhibit cancer cells, inhibit NF-κB pathway and induce ROS, and have potential as anticancer compounds. Full article
(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)
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Open AccessArticle Constituents of Psoralea corylifolia Fruits and Their Effects on Methicillin-Resistant Staphylococcus aureus
Molecules 2015, 20(7), 12500-12511; doi:10.3390/molecules200712500
Received: 1 June 2015 / Revised: 1 July 2015 / Accepted: 2 July 2015 / Published: 9 July 2015
Cited by 2 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new flavonoids, bakuisoflavone (1) and bakuflavanone (2), together with 15 known compounds, were isolated from the fruits of Psoralea corylifolia, and their structures were characterized by spectroscopic data. The effects of the isolated compounds on methicillin-resistant Staphylococcus
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Two new flavonoids, bakuisoflavone (1) and bakuflavanone (2), together with 15 known compounds, were isolated from the fruits of Psoralea corylifolia, and their structures were characterized by spectroscopic data. The effects of the isolated compounds on methicillin-resistant Staphylococcus aureus were also examined. We found that two compounds, isobavachalcone (10) and bakuchiol (12), showed noticeable antibacterial effects on the MRSA strains examined. Quantitation of the major constituents, including anti-MRSA constituents, was then performed. The results showed individual contents of 1.26%–16.49% (w/w) among the examined compounds in the ethyl acetate extract from P. corylifolia fruits. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Pro-Angiogenic Effects of Chalcone Derivatives in Zebrafish Embryos in Vivo
Molecules 2015, 20(7), 12512-12524; doi:10.3390/molecules200712512
Received: 20 April 2015 / Revised: 3 July 2015 / Accepted: 6 July 2015 / Published: 9 July 2015
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Abstract
The aim of this study was to investigate novel chalcones with potent angiogenic activities in vivo. Chalcone-based derivatives were evaluated using a transgenic zebrafish line with fluorescent vessels to real-time monitor the effect on angiogenesis. Results showed that the chalcone analogues did
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The aim of this study was to investigate novel chalcones with potent angiogenic activities in vivo. Chalcone-based derivatives were evaluated using a transgenic zebrafish line with fluorescent vessels to real-time monitor the effect on angiogenesis. Results showed that the chalcone analogues did not possess anti-angiogenic effect on zebrafish vasculatures; instead, some of them displayed potent pro-angiogenic effects on the formation of the sub-intestinal vein. Similar pro-angiogenic effects can also be seen on wild type zebrafish embryos. Moreover, the expression of vegfa, the major regulator for angiogenesis, was also upregulated in their treatment. Taken together, we have synthesized and identified a series of novel chalcone-based derivatives as potent in vivo pro-angiogenic compounds. These novel compounds hold potential for therapeutic angiogenesis. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Microbiological Assessment, Nutritional Characterization and Phenolic Compounds of Bee Pollen from Mellipona mandacaia Smith, 1983
Molecules 2015, 20(7), 12525-12544; doi:10.3390/molecules200712525
Received: 4 June 2015 / Revised: 30 June 2015 / Accepted: 3 July 2015 / Published: 9 July 2015
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Abstract
This study aims to assess the microbiological parameters and the chemical composition of 21 samples of stingless bee pollen (Melipona mandacaia) from two regions of Bahia, Brazil (João Dourado and Uibaí), with particular emphasis on the nutritional value, total phenols and
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This study aims to assess the microbiological parameters and the chemical composition of 21 samples of stingless bee pollen (Melipona mandacaia) from two regions of Bahia, Brazil (João Dourado and Uibaí), with particular emphasis on the nutritional value, total phenols and flavonoids and fatty acids composition. Regarding the microbiological quality, the studied microorganisms (moulds and yeasts, coliforms, Escherichia coli, Staphylococcus aureus, Salmonella sp., psychrotrophic and sulfite-reducing Clostridia) were absent in all samples. On the other hand, the values obtained for the aerobic mesophilic microorganism ranged from 11.0 ± 1.0 to 1.32 ± 1.2 cfu∙g1 (JD samples) and from 282 ± 3.82 to 688 ± 10.1 cfu∙g1 (U samples). The nutritional parameters (moisture, ash, water activity, pH, total acidity, protein, fiber, total phenolic, flavonoids and reducing sugars) were within the stipulated by law, except for pH and moisture content, which presented superior and inferior values, respectively. Polyunsaturated fatty acids (54.1%) were significantly higher than saturated (42.18%) and monounsaturated (3.71%). It was found that the bee pollen is safe from the microbiological point of view and has a good nutritional quality. The influence of the geographical origin on the assessed parameters was evident, especially concerning the fatty acid profile. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Acerogenin A from Acer nikoense Maxim Prevents Oxidative Stress-Induced Neuronal Cell Death through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse Hippocampal HT22 Cell Line
Molecules 2015, 20(7), 12545-12557; doi:10.3390/molecules200712545
Received: 27 May 2015 / Revised: 2 July 2015 / Accepted: 7 July 2015 / Published: 9 July 2015
Cited by 6 | PDF Full-text (1329 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases.
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Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases. The stem bark of Acer nikoense Maxim (Aceraceae) is indigenous to Japan; it has been used in folk medicine as a treatment of hepatic disorders and eye diseases. Acerogenin A, a natural compound isolated from Japanese folk medicine A. nikoense, showed neuroprotective effects and reactive oxygen species (ROS) reduction on glutamate-induced neurotoxicity by inducing the expression of HO-1 in mouse hippocampal HT22 cells. Furthermore, acerogenin A caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and the activation of the PI3K/AKT signaling pathways. In this study, we demonstrated that acerogenin A effectively prevents glutamate-induced oxidative damage, and HO-1 induction via PI3K/Akt and Nrf2 pathways appears to play a key role in the protection of HT22 cells. Therefore, this study implies that the Nrf2/HO-1 pathway represents a biological target and that acerogenin A might be a candidate for the prevention of neurodegeneration. Full article
Open AccessArticle CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells
Molecules 2015, 20(7), 12576-12589; doi:10.3390/molecules200712576
Received: 28 May 2015 / Revised: 4 July 2015 / Accepted: 7 July 2015 / Published: 10 July 2015
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Abstract
Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously
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Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53). With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations) in a more specific and targeted fashion. Full article
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Open AccessArticle Development of Guanidine-Bisurea Bifunctional Organocatalysts with a Chiral Pyrrolidine Moiety and Application to α-Hydroxylation of Tetralone-Derived β-Keto Esters
Molecules 2015, 20(7), 12590-12598; doi:10.3390/molecules200712590
Received: 5 June 2015 / Revised: 5 July 2015 / Accepted: 6 July 2015 / Published: 10 July 2015
Cited by 1 | PDF Full-text (816 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel guanidine-bisurea bifunctional organocatalysts 5 bearing a chiral pyrrolidine moiety on guanidine were designed with the guidance of DFT calculations. The resulting organocatalysts 5 were examined for α-hydroxylation of tetralone-derived β-keto esters, and good selectivity was obtained with 5j bearing a methoxymethyl ether-containing
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Novel guanidine-bisurea bifunctional organocatalysts 5 bearing a chiral pyrrolidine moiety on guanidine were designed with the guidance of DFT calculations. The resulting organocatalysts 5 were examined for α-hydroxylation of tetralone-derived β-keto esters, and good selectivity was obtained with 5j bearing a methoxymethyl ether-containing chiral pyrrolidine moiety. Full article
(This article belongs to the Special Issue Brønsted Base Catalysis in Organic Synthesis)
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Open AccessArticle Simultaneous Fitting of Absorption Spectra and Their Second Derivatives for an Improved Analysis of Protein Infrared Spectra
Molecules 2015, 20(7), 12599-12622; doi:10.3390/molecules200712599
Received: 7 May 2015 / Revised: 6 July 2015 / Accepted: 7 July 2015 / Published: 10 July 2015
Cited by 5 | PDF Full-text (1501 KB) | HTML Full-text | XML Full-text
Abstract
Infrared spectroscopy is a powerful tool in protein science due to its sensitivity to changes in secondary structure or conformation. In order to take advantage of the full power of infrared spectroscopy in structural studies of proteins, complex band contours, such as the
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Infrared spectroscopy is a powerful tool in protein science due to its sensitivity to changes in secondary structure or conformation. In order to take advantage of the full power of infrared spectroscopy in structural studies of proteins, complex band contours, such as the amide I band, have to be decomposed into their main component bands, a process referred to as curve fitting. In this paper, we report on an improved curve fitting approach in which absorption spectra and second derivative spectra are fitted simultaneously. Our approach, which we name co-fitting, leads to a more reliable modelling of the experimental data because it uses more spectral information than the standard approach of fitting only the absorption spectrum. It also avoids that the fitting routine becomes trapped in local minima. We have tested the proposed approach using infrared absorption spectra of three mixed α/β proteins with different degrees of spectral overlap in the amide I region: ribonuclease A, pyruvate kinase, and aconitase. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
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Open AccessArticle Non-Nucleosidic Analogues of Polyaminonucleosides and Their Influence on Thermodynamic Properties of Derived Oligonucleotides
Molecules 2015, 20(7), 12652-12669; doi:10.3390/molecules200712652
Received: 17 March 2015 / Revised: 8 July 2015 / Accepted: 9 July 2015 / Published: 13 July 2015
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Abstract
The rationale for the synthesis of cationic modified nucleosides is higher expected nuclease resistance and potentially better cellular uptake due to an overall reduced negative charge based on internal charge compensation. Due to the ideal distance between cationic groups, polyamines are perfect counterions
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The rationale for the synthesis of cationic modified nucleosides is higher expected nuclease resistance and potentially better cellular uptake due to an overall reduced negative charge based on internal charge compensation. Due to the ideal distance between cationic groups, polyamines are perfect counterions for oligodeoxyribonucleotides. We have synthesized non-nucleosidic analogues built from units that carry different diol structures instead of sugar residues and functionalized with polyamines. The non-nucleosidic analogues were attached as internal or 5′-terminal modifications in oligodeoxyribonucleotide strands. The thermodynamic studies of these polyaminooligonucleotide analogues revealed stabilizing or destabilizing effects that depend on the linker or polyamine used. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Synthesis, Structure and Antioxidant Activity of Cyclohexene-Fused Selenuranes and Related Derivatives
Molecules 2015, 20(7), 12670-12685; doi:10.3390/molecules200712670
Received: 30 April 2015 / Revised: 30 June 2015 / Accepted: 6 July 2015 / Published: 13 July 2015
Cited by 3 | PDF Full-text (1689 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synthesis, structure and antioxidant activity of new cyclohexene-fused spiroselenuranes and a spirotellurane is reported. Oxidation reactions of bis(o-formylcyclohex- 1-ene)selenide/bis(2-hydroxymethylcyclohex-1-ene)selenide provide the corresponding spiroselenuranes. The glutathione peroxidase-like activity of the newly synthesized compounds has been evaluated. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Cu and Boron Doped Carbon Nitride for Highly Selective Oxidation of Toluene to Benzaldehyde
Molecules 2015, 20(7), 12686-12697; doi:10.3390/molecules200712686
Received: 29 May 2015 / Revised: 25 June 2015 / Accepted: 8 July 2015 / Published: 13 July 2015
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Abstract
A novel Cu and boron doped graphitic carbon nitride catalyst (Cu-CNB) was synthesized using cheap precursors and systematically characterized. The selective oxidation of toluene proceeded very smoothly over the catalyst at 70 °C using tert-butyl hydroperoxide (TBHP) as the oxidant to exclusively afford
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A novel Cu and boron doped graphitic carbon nitride catalyst (Cu-CNB) was synthesized using cheap precursors and systematically characterized. The selective oxidation of toluene proceeded very smoothly over the catalyst at 70 °C using tert-butyl hydroperoxide (TBHP) as the oxidant to exclusively afford benzaldehyde. The catalyst can be used for at least five cycles without decrease in activity and selectivity. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Neolignans from Nectandra megapotamica (Lauraceae) Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells
Molecules 2015, 20(7), 12757-12768; doi:10.3390/molecules200712757
Received: 8 June 2015 / Revised: 30 June 2015 / Accepted: 2 July 2015 / Published: 15 July 2015
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Abstract
Nectandra megapotamica (Spreng.) Mez. (Lauraceae) is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification
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Nectandra megapotamica (Spreng.) Mez. (Lauraceae) is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae) leaves using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1), machilin-G (2), machilin-I (3), aristolignin (4), nectandrin A (5), veraguensin (6), ganschisandrin (7), and galgravin (8). Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s) related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 µg/mL, respectively, against human leukemia (HL-60) tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Virtual Screening and Molecular Dynamics Study of Potential Negative Allosteric Modulators of mGluR1 from Chinese Herbs
Molecules 2015, 20(7), 12769-12786; doi:10.3390/molecules200712769
Received: 28 April 2015 / Revised: 25 June 2015 / Accepted: 9 July 2015 / Published: 15 July 2015
Cited by 9 | PDF Full-text (2950 KB) | HTML Full-text | XML Full-text
Abstract
The metabotropic glutamate subtype 1 (mGluR1), a member of the metabotropic glutamate receptors, is a therapeutic target for neurological disorders. However, due to the lower subtype selectivity of mGluR1 orthosteric compounds, a new targeted strategy, known as allosteric modulators research, is needed for
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The metabotropic glutamate subtype 1 (mGluR1), a member of the metabotropic glutamate receptors, is a therapeutic target for neurological disorders. However, due to the lower subtype selectivity of mGluR1 orthosteric compounds, a new targeted strategy, known as allosteric modulators research, is needed for the treatment of mGluR1-related diseases. Recently, the structure of the seven-transmembrane domain (7TMD) of mGluR1 has been solved, which reveals the binding site of allosteric modulators and provides an opportunity for future subtype-selectivity drug design. In this study, a series of computer-aided drug design methods were utilized to discover potential mGluR1 negative allosteric modulators (NAMs). Pharmacophore models were constructed based on three different structure types of mGluR1 NAMs. After validation using the built-in parameters and test set, the optimal pharmacophore model of each structure type was selected and utilized as a query to screen the Traditional Chinese Medicine Database (TCMD). Then, three different hit lists of compounds were obtained. Molecular docking was used based on the latest crystal structure of mGluR1-7TMD to further filter these hits. As a compound with high QFIT and LibDock Score was preferred, a total of 30 compounds were retained. MD simulation was utilized to confirm the stability of potential compounds binding. From the computational results, thesinine-4ʹ-O-β-d-glucoside, nigrolineaxanthone-P and nodakenin might exhibit negative allosteric moderating effects on mGluR1. This paper indicates the applicability of molecular simulation technologies for discovering potential natural mGluR1 NAMs from Chinese herbs. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Structure Elucidation of Procyanidins Isolated from Rhododendron formosanum and Their Anti-Oxidative and Anti-Bacterial Activities
Molecules 2015, 20(7), 12787-12803; doi:10.3390/molecules200712787
Received: 4 June 2015 / Revised: 3 July 2015 / Accepted: 13 July 2015 / Published: 15 July 2015
Cited by 7 | PDF Full-text (1737 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rhododendron formosanum is an endemic species distributed in the central mountains of Taiwan. In this study, the biological activities of major procyanidins isolated from the leaf extract of R. formosanum were investigated. Four compounds, including two procyanidin dimers, procyanidin A1 (1)
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Rhododendron formosanum is an endemic species distributed in the central mountains of Taiwan. In this study, the biological activities of major procyanidins isolated from the leaf extract of R. formosanum were investigated. Four compounds, including two procyanidin dimers, procyanidin A1 (1) and B3 (2), and two procyanidin trimmers, procyanidin C4 (4) and cinnamtannin D1 (5), were isolated and identified on the basis of spectroscopic data. The structure of a new procyanidin dimer, rhodonidin A (3), was elucidated by 2D-NMR, CD spectrum and MS. The procyanidin trimmers and rhodonidin A are reported for the first time in Ericaceae. The biological activities of these procyanidins were evaluated using anti-bacterial and anti-oxidative assays. Only the new compound 3 demonstrated strong anti-bacterial activity against Staphylococcus aureus at an MIC value of 4 μg/mL. All compounds showed pronounced antioxidant activities and the activities are enhanced as the amount of OH groups in procyanidins increased. In conclusion, the pleiotropic effects of procyanidins isolated from the leaves of R. formosanum can be a source of promising compounds for the development of future pharmacological applications. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle 7-Epiclusianone, a Benzophenone Extracted from Garcinia brasiliensis (Clusiaceae), Induces Cell Cycle Arrest in G1/S Transition in A549 Cells
Molecules 2015, 20(7), 12804-12816; doi:10.3390/molecules200712804
Received: 16 May 2015 / Revised: 23 June 2015 / Accepted: 8 July 2015 / Published: 15 July 2015
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Abstract
Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant
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Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 μM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Three-Dimensional Compound Comparison Methods and Their Application in Drug Discovery
Molecules 2015, 20(7), 12841-12862; doi:10.3390/molecules200712841
Received: 6 May 2015 / Revised: 7 July 2015 / Accepted: 13 July 2015 / Published: 16 July 2015
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Abstract
Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS) methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target
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Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS) methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target receptor and that they are faster than structure-based methods. LBVS methods can be classified based on the complexity of ligand structure information utilized: one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D). Unlike 1D and 2D methods, 3D methods can have enhanced performance since they treat the conformational flexibility of compounds. In this paper, a number of 3D methods will be reviewed. In addition, four representative 3D methods were benchmarked to understand their performance in virtual screening. Specifically, we tested overall performance in key aspects including the ability to find dissimilar active compounds, and computational speed. Full article
(This article belongs to the Special Issue Chemoinformatics)
Open AccessArticle Dual Radiolabeling as a Technique to Track Nanocarriers: The Case of Gold Nanoparticles
Molecules 2015, 20(7), 12863-12879; doi:10.3390/molecules200712863
Received: 23 May 2015 / Revised: 22 June 2015 / Accepted: 10 July 2015 / Published: 16 July 2015
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Abstract
Gold nanoparticles (AuNPs) have shown great potential for use in nanomedicine and nanotechnologies due to their ease of synthesis and functionalization. However, their apparent biocompatibility and biodistribution is still a matter of intense debate due to the lack of clear safety data. To
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Gold nanoparticles (AuNPs) have shown great potential for use in nanomedicine and nanotechnologies due to their ease of synthesis and functionalization. However, their apparent biocompatibility and biodistribution is still a matter of intense debate due to the lack of clear safety data. To investigate the biodistribution of AuNPs, monodisperse 14-nm dual-radiolabeled [14C]citrate-coated [198Au]AuNPs were synthesized and their physico-chemical characteristics compared to those of non-radiolabeled AuNPs synthesized by the same method. The dual-radiolabeled AuNPs were administered to rats by oral or intravenous routes. After 24 h, the amounts of Au core and citrate surface coating were quantified using gamma spectroscopy for 198Au and liquid scintillation for the 14C. The Au core and citrate surface coating had different biodistribution profiles in the organs/tissues analyzed, and no oral absorption was observed. We conclude that the different components of the AuNPs system, in this case the Au core and citrate surface coating, did not remain intact, resulting in the different distribution profiles observed. A better understanding of the biodistribution profiles of other surface attachments or cargo of AuNPs in relation to the Au core is required to successfully use AuNPs as drug delivery vehicles. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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Open AccessArticle Characteristic Conformation of Mosher’s Amide Elucidated Using the Cambridge Structural Database
Molecules 2015, 20(7), 12880-12900; doi:10.3390/molecules200712880
Received: 23 June 2015 / Revised: 9 July 2015 / Accepted: 10 July 2015 / Published: 16 July 2015
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Abstract
Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from –30° to
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Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from –30° to 0° with an average angle θ1 of −13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O–Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Enantioselective Solvent-Free Synthesis of 3-Alkyl-3-hydroxy-2-oxoindoles Catalyzed by Binam-Prolinamides
Molecules 2015, 20(7), 12901-12912; doi:10.3390/molecules200712901
Received: 15 June 2015 / Revised: 6 July 2015 / Accepted: 10 July 2015 / Published: 16 July 2015
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Abstract
BINAM-prolinamides are very efficient catalyst for the synthesis of non-protected and N-benzyl isatin derivatives by using an aldol reaction between ketones and isatins under solvent-free conditions. The results in terms of diastereo- and enantioselectivities are good, up to 99% de and 97%
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BINAM-prolinamides are very efficient catalyst for the synthesis of non-protected and N-benzyl isatin derivatives by using an aldol reaction between ketones and isatins under solvent-free conditions. The results in terms of diastereo- and enantioselectivities are good, up to 99% de and 97% ee, and higher to those previously reported in the literature under similar reaction conditions. A high variation of the results is observed depending on the structure of the isatin and the ketone used in the process. While 90% of ee and 97% ee, respectively, is obtained by using (Ra)-BINAM-l-(bis)prolinamide as catalyst in the addition of cyclohexanone and α-methoxyacetone to free isatin, 90% ee is achieved for the reaction between N-benzyl isatin and acetone using N-tosyl BINAM-l-prolinamide as catalyst. This reaction is also carried out using a silica BINAM-l-prolinamide supported catalyst under solvent-free conditions, which can be reused up to five times giving similar results. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle Sumac Silver Novel Biodegradable Nano Composite for Bio-Medical Application: Antibacterial Activity
Molecules 2015, 20(7), 12946-12958; doi:10.3390/molecules200712946
Received: 28 April 2015 / Revised: 23 June 2015 / Accepted: 24 June 2015 / Published: 17 July 2015
Cited by 8 | PDF Full-text (3278 KB) | HTML Full-text | XML Full-text
Abstract
The development of reliable and ecofriendly approaches for the production of nanomaterials is a significant aspect of nanotechnology nowadays. One of the most important methods, which shows enormous potential, is based on the green synthesis of nanoparticles using plant extract. In this paper,
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The development of reliable and ecofriendly approaches for the production of nanomaterials is a significant aspect of nanotechnology nowadays. One of the most important methods, which shows enormous potential, is based on the green synthesis of nanoparticles using plant extract. In this paper, we aimed to develop a rapid, environmentally friendly process for the synthesis silver nanoparticles using aqueous extract of sumac. The bioactive compounds of sumac extract seem to play a role in the synthesis and capping of silver nanoparticles. Structural, morphological and optical properties of the nanoparticles were characterized using FTIR, XRD, FESEM and UV-Vis spectroscopy. The formation of Ag-NP was immediate within 10 min and confirmed with an absorbance band centered at 438 nm. The mean particle size for the green synthesized silver nanoparticles is 19.81 ± 3.67 nm and is fairly stable with a zeta potential value of −32.9 mV. The bio-formed Ag-NPs were effective against E. coli with a maximum inhibition zone of 14.3 ± 0.32 mm. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Substituent Effects on the Stability and Antioxidant Activity of Spirodiazaselenuranes
Molecules 2015, 20(7), 12959-12978; doi:10.3390/molecules200712959
Received: 18 June 2015 / Revised: 8 July 2015 / Accepted: 14 July 2015 / Published: 17 July 2015
Cited by 1 | PDF Full-text (1054 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Spirodiazaselenuranes are structurally interesting compounds and the stability of these compounds depends highly on the nature of the substituents attached to the nitrogen atoms. Aromatic substituents are known to play important roles in stabilizing the Se-N bonds in spiro compounds. In this study,
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Spirodiazaselenuranes are structurally interesting compounds and the stability of these compounds depends highly on the nature of the substituents attached to the nitrogen atoms. Aromatic substituents are known to play important roles in stabilizing the Se-N bonds in spiro compounds. In this study, several spirodiazaselenuranes are synthesized by introducing benzylic and aliphatic substituents to understand their effect on the stability of the Se-N bonds and the antioxidant activity. Replacement of phenyl substituent by benzyl/alkyl groups significantly reduces the stability of the spirodiazaselenuranes and slows down the oxidative cyclization process. The selenium centre in the spiro compounds undergoes further oxidation to produce the corresponding selenurane oxides, which are stable at room temperature. Comparison of the glutathione peroxidase (GPx) mimetic activity of the compounds showed that the diaryl selenides having heterocyclic rings are significantly more active due to the facile oxidation of the selenium centre. However, the activity is reduced significantly for compounds having aliphatic substituents. In addition to GPx activity, the compounds also inhibit peroxynitrite-mediated nitration and oxidation reaction of protein and small molecules, respectively. The experimental observations suggest that the antioxidant activity is increased considerably upon substitution of the aromatic group with the benzylic/aliphatic substituents on the nitrogen atoms. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Chloro({2-[mesityl(quinolin-8-yl-κN)boryl]-3,5-dimethyl-phenyl}methyl-κC)palladium(II) as a Catalyst for Heck Reactions
Molecules 2015, 20(7), 12979-12991; doi:10.3390/molecules200712979
Received: 1 May 2015 / Revised: 9 July 2015 / Accepted: 15 July 2015 / Published: 17 July 2015
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Abstract
We recently reported an air and moisture stable 16-electron borapalladacycle formed upon combination of 8-quinolyldimesitylborane with bis(benzonitrile)dichloropalladium(II). The complex features a tucked mesityl group formed upon metalation of an ortho-methyl group on a mesityl; however it is unusually stable due to contribution
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We recently reported an air and moisture stable 16-electron borapalladacycle formed upon combination of 8-quinolyldimesitylborane with bis(benzonitrile)dichloropalladium(II). The complex features a tucked mesityl group formed upon metalation of an ortho-methyl group on a mesityl; however it is unusually stable due to contribution of the boron pz orbital in delocalizing the carbanion that gives rise to an η4-boratabutadiene fragment coordinated to Pd(II), as evidenced from crystallographic data. This complex was observed to be a highly active catalyst for the Heck reaction. Data of the catalyst activity are presented alongside data found in the literature, and initial comparison reveals that the borapalladacycle is quite active. The observed catalysis suggests the borapalladacycle readily undergoes reductive elimination; however the Pd(0) complex has not yet been isolated. Nevertheless, the ambiphilic ligand 8-quinolyldimesitylborane may be able to support palladium in different redox states. Full article
(This article belongs to the Special Issue The Reactivity of Frustrated Lewis Pairs)
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Open AccessArticle Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells
Molecules 2015, 20(7), 12992-13004; doi:10.3390/molecules200712992
Received: 29 May 2015 / Revised: 13 July 2015 / Accepted: 14 July 2015 / Published: 17 July 2015
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Abstract
Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the
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Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits. Full article
Open AccessArticle Bioaccumulation of Trace Metals in Mussel (Mytilus galloprovincialis) from Mali Ston Bay during DSP Toxicity Episodes
Molecules 2015, 20(7), 13031-13040; doi:10.3390/molecules200713031
Received: 19 May 2015 / Revised: 13 July 2015 / Accepted: 13 July 2015 / Published: 17 July 2015
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Abstract
The Croatian National Monitoring Program revealed the presence of Diarrhetic Shellfish Poisoning (DSP) toxicity in Mediterranean blue mussel (Mytilus galloprovincialis) from breeding farms in southern Adriatic Sea through January to June 2011. The mouse bioassay tests (MBA; at the time the
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The Croatian National Monitoring Program revealed the presence of Diarrhetic Shellfish Poisoning (DSP) toxicity in Mediterranean blue mussel (Mytilus galloprovincialis) from breeding farms in southern Adriatic Sea through January to June 2011. The mouse bioassay tests (MBA; at the time the official method for DSP toxins) were accompanied by atypical symptomatology in the animals and this caused doubts about the assay results. Consequently, in parallel studies reported here, the concentration of Cd, Cr, Cu, Ni, Pb and Zn in soft tissue of DSP positive and negative mussels samples was determined. Cd, Cr, Zn and Ni show higher values in approximately 75% of the DSP positive samples, whereas for Pb and Cr the values were 26% and 34%, respectively. This trend was unchanged during the whole observation period. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver
Molecules 2015, 20(7), 13041-13054; doi:10.3390/molecules200713041
Received: 14 May 2015 / Revised: 8 July 2015 / Accepted: 10 July 2015 / Published: 20 July 2015
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Abstract
This study provides the scientific basis for the anti-inflammatory effects of licorice extract in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage model and the effects of its ingredients, glycyrrhizic acid (GA), liquiritin (LQ) and liquiritigenin (LG), in a lipopolysaccharide (LPS)-stimulated
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This study provides the scientific basis for the anti-inflammatory effects of licorice extract in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage model and the effects of its ingredients, glycyrrhizic acid (GA), liquiritin (LQ) and liquiritigenin (LG), in a lipopolysaccharide (LPS)-stimulated microglial cell model. The GA, LQ and LG inhibited the LPS-stimulated elevation of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and interleukin (IL)-6 in BV2 (mouse brain microglia) cells. Furthermore, licorice extract inhibited the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in the livers of t-BHP-treated mice models. This result suggested that mechanistic-based evidence substantiating the traditional claims of licorice extract and its three bioactive components can be applied for the treatment of inflammation-related disorders, such as oxidative liver damage and inflammation diseases. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle New Fluorescence Probes for Biomolecules
Molecules 2015, 20(7), 13071-13079; doi:10.3390/molecules200713071
Received: 12 June 2015 / Revised: 8 July 2015 / Accepted: 9 July 2015 / Published: 20 July 2015
Cited by 4 | PDF Full-text (1115 KB) | HTML Full-text | XML Full-text
Abstract
Steady state fluorescence measurements have been used for the investigation of interaction between the bovine serum albumin (BSA) and fluorescence probes: 3-hydroxy-2,4- bis[(3-methyl-1,3-benzoxazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ6), 3-hydroxy- 2,4-bis[(3-methyl-1,3-benzothiazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ7) and 3-hydroxy-2,4-bis[(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)methyl]cyclobut-2-en-1-one (SQ8). The binding constant between bovine serum albumin
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Steady state fluorescence measurements have been used for the investigation of interaction between the bovine serum albumin (BSA) and fluorescence probes: 3-hydroxy-2,4- bis[(3-methyl-1,3-benzoxazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ6), 3-hydroxy- 2,4-bis[(3-methyl-1,3-benzothiazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ7) and 3-hydroxy-2,4-bis[(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)methyl]cyclobut-2-en-1-one (SQ8). The binding constant between bovine serum albumin and squarine dyes has been determined by using both the Benesi-Hildebrand and Stern-Volmer equations. The negative value of free energy change indicates the existence of a spontaneous complexation process of BSA with squarine dyes. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessCommunication The Complete Chloroplast Genome of Capsicum annuum var. glabriusculum Using Illumina Sequencing
Molecules 2015, 20(7), 13080-13088; doi:10.3390/molecules200713080
Received: 22 May 2015 / Revised: 6 July 2015 / Accepted: 16 July 2015 / Published: 20 July 2015
Cited by 4 | PDF Full-text (906 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chloroplast (cp) genome sequences provide a valuable source for DNA barcoding. Molecular phylogenetic studies have concentrated on DNA sequencing of conserved gene loci. However, this approach is time consuming and more difficult to implement when gene organization differs among species. Here we report
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Chloroplast (cp) genome sequences provide a valuable source for DNA barcoding. Molecular phylogenetic studies have concentrated on DNA sequencing of conserved gene loci. However, this approach is time consuming and more difficult to implement when gene organization differs among species. Here we report the complete re-sequencing of the cp genome of Capsicum pepper (Capsicum annuum var. glabriusculum) using the Illumina platform. The total length of the cp genome is 156,817 bp with a 37.7% overall GC content. A pair of inverted repeats (IRs) of 50,284 bp were separated by a small single copy (SSC; 18,948 bp) and a large single copy (LSC; 87,446 bp). The number of cp genes in C. annuum var. glabriusculum is the same as that in other Capsicum species. Variations in the lengths of LSC; SSC and IR regions were the main contributors to the size variation in the cp genome of this species. A total of 125 simple sequence repeat (SSR) and 48 insertions or deletions variants were found by sequence alignment of Capsicum cp genome. These findings provide a foundation for further investigation of cp genome evolution in Capsicum and other higher plants. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Identification and Expression Analysis of Glucosinolate Biosynthetic Genes and Estimation of Glucosinolate Contents in Edible Organs of Brassica oleracea Subspecies
Molecules 2015, 20(7), 13089-13111; doi:10.3390/molecules200713089
Received: 25 June 2015 / Revised: 11 July 2015 / Accepted: 16 July 2015 / Published: 20 July 2015
Cited by 12 | PDF Full-text (1524 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glucosinolates are anti-carcinogenic, anti-oxidative biochemical compounds that defend plants from insect and microbial attack. Glucosinolates are abundant in all cruciferous crops, including all vegetable and oilseed Brassica species. Here, we studied the expression of glucosinolate biosynthesis genes and determined glucosinolate contents in the
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Glucosinolates are anti-carcinogenic, anti-oxidative biochemical compounds that defend plants from insect and microbial attack. Glucosinolates are abundant in all cruciferous crops, including all vegetable and oilseed Brassica species. Here, we studied the expression of glucosinolate biosynthesis genes and determined glucosinolate contents in the edible organs of a total of 12 genotypes of Brassica oleracea: three genotypes each from cabbage, kale, kohlrabi and cauliflower subspecies. Among the 81 genes analyzed by RT-PCR, 19 are transcription factor-related, two different sets of 25 genes are involved in aliphatic and indolic biosynthesis pathways and the rest are breakdown-related. The expression of glucosinolate-related genes in the stems of kohlrabi was remarkably different compared to leaves of cabbage and kale and florets of cauliflower as only eight genes out of 81 were expressed in the stem tissues of kohlrabi. In the stem tissue of kohlrabi, only one aliphatic transcription factor-related gene, Bol036286 (MYB28) and one indolic transcription factor-related gene, Bol030761 (MYB51), were expressed. The results indicated the expression of all genes is not essential for glucosinolate biosynthesis. Using HPLC analysis, a total of 16 different types of glucosinolates were identified in four subspecies, nine of them were aliphatic, four of them were indolic and one was aromatic. Cauliflower florets measured the highest number of 14 glucosinolates. Among the aliphatic glucosinolates, only gluconapin was found in the florets of cauliflower. Glucoiberverin and glucobrassicanapin contents were the highest in the stems of kohlrabi. The indolic methoxyglucobrassicin and aromatic gluconasturtiin accounted for the highest content in the florets of cauliflower. A further detailed investigation and analyses is required to discern the precise roles of each of the genes for aliphatic and indolic glucosinolate biosynthesis in the edible organs. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle The Influence of the Combination of Carboxylate and Phosphinate Pendant Arms in 1,4,7-Triazacyclononane-Based Chelators on Their 68Ga Labelling Properties
Molecules 2015, 20(7), 13112-13126; doi:10.3390/molecules200713112
Received: 10 May 2015 / Revised: 10 July 2015 / Accepted: 13 July 2015 / Published: 21 July 2015
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Abstract
In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn) derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups towards 68Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid (NOPA) and 1,4,7- triazacyclononane-4,7-diacetic-1-[methylene(2-carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions with trivalent or pentavalent forms of H-phosphinic
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In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn) derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups towards 68Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid (NOPA) and 1,4,7- triazacyclononane-4,7-diacetic-1-[methylene(2-carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions with trivalent or pentavalent forms of H-phosphinic acids as phosphorus components. Stepwise protonation constants logK1–3 12.06, 3.90 and 1.95, and stability constants with GaIII and CuII, logKGaL 24.01 and logKCuL 16.66, were potentiometrically determined for NOPA. Both ligands were labelled with 68Ga and compared with NOTA (tacn-N,N′,N-triacetic acid) and NOPO, a TRAP-type [tacn-N,N′,N- tris(methylenephosphinic acid)] chelator. At pH 3, NOPO and NOPA showed higher labelling efficiency (binding with lower ligand excess) at both room temperature and 95 °C, compared to NO2AP and NOTA. Labelling efficiency at pH = 0–3 correlated with a number of phosphinic acid pendants: NOPO >> NOPA > NO2AP >> NOTA; however, it was more apparent at 95 °C than at room temperature. By contrast, NOTA was found to be labelled more efficiently at pH > 4 compared to the ligands with phosphinic acids. Overall, replacement of a single phosphinate donor with a carboxylate does not challenge 68Ga labelling of TRAP-type chelators. However, the presence of carboxylates facilitates labelling at neutral or weakly acidic pH. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessArticle A New Furofuran Lignan Diglycoside and Other Secondary Metabolites from the Antidepressant Extract of Castilleja tenuiflora Benth
Molecules 2015, 20(7), 13127-13143; doi:10.3390/molecules200713127
Received: 3 June 2015 / Revised: 10 July 2015 / Accepted: 13 July 2015 / Published: 21 July 2015
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Abstract
Castilleja tenuiflora has been used for the treatment of several Central Nervous System (CNS) diseases. Herein we report the antidepressant activity of the methanol extract from the leaves of this medicinal plant. The oral administration of MeOH extract (500 mg/kg) induced a significant
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Castilleja tenuiflora has been used for the treatment of several Central Nervous System (CNS) diseases. Herein we report the antidepressant activity of the methanol extract from the leaves of this medicinal plant. The oral administration of MeOH extract (500 mg/kg) induced a significant (p < 0.05) decrement of the immobility parameter on Forced Swimming Test (FST) and an increment in the latency and duration of the hypnosis, induced by administration of sodium pentobarbital (Pbi, 40 mg/kg, i.p.). Chemical analysis of this antidepressant extract allowed the isolation of (+)-piperitol-4-O-xylopyranosyl-(1→6)-O-glucopyranoside. This new furofuran lignan diglycoside was named tenuifloroside (1) and its complete chemical structure elucidation on the basis of 1D and 2D NMR spectra analysis of the natural compound 1 and its peracetylated derivative 1a is described. This compound was found together with two flavones—apigenin and luteolin 5-methyl ether—a phenylethanoid—verbascoside—and three iridoids—geniposide, caryoptoside and aucubin. All these compounds were purified by successive normal and reverse phase column chromatography. Tenuifloroside, caryoptoside and luteolin 5-methyl ether were isolated from Castilleja genus for the first time. These findings demonstrate that C. tenuiflora methanol extract has beneficial effect on depressive behaviors, and the knowledge of its chemical constitution allows us to propose a new standardized treatment for future investigations of this species in depressive illness. Full article
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Open AccessArticle Molecular Docking and Multivariate Analysis of Xanthones as Antimicrobial and Antiviral Agents
Molecules 2015, 20(7), 13165-13204; doi:10.3390/molecules200713165
Received: 1 April 2015 / Revised: 10 May 2015 / Accepted: 21 May 2015 / Published: 21 July 2015
Cited by 2 | PDF Full-text (4535 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Xanthones are secondary metabolites which have drawn considerable interest over the last decades due to their antimicrobial properties, among others. A great number of this kind of compounds has been therefore reported, but there is a limited amount of studies on screening for
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Xanthones are secondary metabolites which have drawn considerable interest over the last decades due to their antimicrobial properties, among others. A great number of this kind of compounds has been therefore reported, but there is a limited amount of studies on screening for biological activity. Thus, as part of our research on antimicrobial agents of natural origin, a set of 272 xanthones were submitted to molecular docking (MD) calculations with a group of seven fungal and two viral enzymes. The results indicated that prenylated xanthones are important hits for inhibition of the analyzed enzymes. The MD scores were also analyzed by multivariate statistics. Important structural details were found to be crucial for the inhibition of the tested enzymes by the xanthones. In addition, the classification of active xanthones can be achieved by statistical analysis on molecular docking scores by an affinity-antifungal activity relationship approach. The obtained results therefore are a suitable starting point for the development of antifungal and antiviral agents based on xanthones. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessArticle New Cembranoid Diterpenes from the Cultured Octocoral Nephthea columnaris
Molecules 2015, 20(7), 13205-13215; doi:10.3390/molecules200713205
Received: 24 June 2015 / Revised: 15 July 2015 / Accepted: 17 July 2015 / Published: 21 July 2015
Cited by 8 | PDF Full-text (875 KB) | HTML Full-text | XML Full-text
Abstract
Two new 15-hydroxycembranoid diterpenes, 2β-hydroxy-7β,8α-epoxynephthenol (1) and 2β-hydroxy-11α,12β-epoxynephthenol (2), were isolated from extracts of the octocoral Nephthea columnaris along with a new natural cembrane, epoxynephthenol (3) and a known sterol, nephalsterol A (4). The structures
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Two new 15-hydroxycembranoid diterpenes, 2β-hydroxy-7β,8α-epoxynephthenol (1) and 2β-hydroxy-11α,12β-epoxynephthenol (2), were isolated from extracts of the octocoral Nephthea columnaris along with a new natural cembrane, epoxynephthenol (3) and a known sterol, nephalsterol A (4). The structures of cembranes 13 were elucidated by spectroscopic methods and comparison of the spectroscopic data with those of related analogues. The cytotoxicity of metabolites 14 against a panel of tumor cells is also described. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Separation of Polyphenols and Caffeine from the Acetone Extract of Fermented Tea Leaves (Camellia sinensis) Using High-Performance Countercurrent Chromatography
Molecules 2015, 20(7), 13216-13225; doi:10.3390/molecules200713216
Received: 8 July 2015 / Revised: 14 July 2015 / Accepted: 16 July 2015 / Published: 21 July 2015
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Abstract
Leaves from Camellia sienensis are a popular natural source of various beverage worldwide, and contain caffeine and polyphenols derived from catechin analogues. In the current study, caffeine (CAF, 1) and three tea polyphenols including (−)-epigallocatechin 3-O-gallate (EGCg, 2), (−)-gallocatechin
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Leaves from Camellia sienensis are a popular natural source of various beverage worldwide, and contain caffeine and polyphenols derived from catechin analogues. In the current study, caffeine (CAF, 1) and three tea polyphenols including (−)-epigallocatechin 3-O-gallate (EGCg, 2), (−)-gallocatechin 3-O-gallate (GCg, 3), and (−)-epicatechin 3-O-gallate (ECg, 4) were isolated and purified by flow-rate gradient high-performance countercurrent chromatography (HPCCC) using a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (1:9:1:9, v/v). Two hundred milligrams of acetone-soluble extract from fermented C. sinensis leaves was separated by HPCCC to give 1 (25.4 mg), 2 (16.3 mg), 3 (11.1 mg) and 4 (4.4 mg) with purities over 98%. The structures of 14 were elucidated by QTOF-MS, as well as 1H- and 13C-NMR, and the obtained data were compared to the previously reported values. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Enhanced Inhibitory Effect of Different Antitumor Agents in Self-Microemulsifying Drug Delivery Systems on Human Cervical Cancer HeLa Cells
Molecules 2015, 20(7), 13226-13239; doi:10.3390/molecules200713226
Received: 5 May 2015 / Revised: 6 July 2015 / Accepted: 7 July 2015 / Published: 21 July 2015
Cited by 6 | PDF Full-text (999 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS
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The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle Synthesis, Spectroscopic Investigations (X-ray, NMR and TD-DFT), Antimicrobial Activity and Molecular Docking of 2,6-Bis(hydroxy(phenyl)methyl)cyclohexanone
Molecules 2015, 20(7), 13240-13263; doi:10.3390/molecules200713240
Received: 11 May 2015 / Revised: 11 July 2015 / Accepted: 13 July 2015 / Published: 21 July 2015
Cited by 3 | PDF Full-text (2323 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN microanalysis, and X-ray crystallography. The molecular structure was also investigated by a set of computational studies and found to be in
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The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN microanalysis, and X-ray crystallography. The molecular structure was also investigated by a set of computational studies and found to be in good agreement with the experimental data obtained from the various spectrophotometric techniques. The antimicrobial activity and molecular docking of the synthesized compound was investigated. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Evaluation of the Cytotoxicity of Structurally Correlated p-Menthane Derivatives
Molecules 2015, 20(7), 13264-13280; doi:10.3390/molecules200713264
Received: 7 May 2015 / Revised: 9 July 2015 / Accepted: 16 July 2015 / Published: 21 July 2015
Cited by 5 | PDF Full-text (1729 KB) | HTML Full-text | XML Full-text
Abstract
Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives.
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Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives. Additionally, analogues of perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to identify the molecular characteristics which contribute to their cytotoxicity, which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines, using the MTT assay. The results of this study showed that (−)-perillaldehyde 8,9-epoxide exhibited the highest percentage inhibition of cell proliferation (GI = 96.32%–99.89%). Perillyl alcohol exhibited high cytotoxic activity (90.92%–95.82%), while (+)-limonene 1,2-epoxide (GI = 58.48%–93.10%), (−)-perillaldehyde (GI = 59.28%–83.03%), and (−)-8-hydroxycarvotanacetone (GI = 61.59%–94.01%) showed intermediate activity. All of the compounds tested were less cytotoxic than perillyl alcohol, except (−)-perillaldehyde 8,9-epoxide (IC50 = 1.75–1.03 µL/mg). In general, replacement of C-C double bonds by epoxide groups in addition to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems to play an important role in cytotoxicity. We have demonstrated the cytotoxic influence of chemical substituents on the p-menthane structure, and analogues of perillyl alcohol. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Antioxidant Activity and Their Major Antioxidant Compounds from Acanthopanax senticosus and A. koreanum
Molecules 2015, 20(7), 13281-13295; doi:10.3390/molecules200713281
Received: 19 May 2015 / Revised: 25 June 2015 / Accepted: 15 July 2015 / Published: 22 July 2015
Cited by 10 | PDF Full-text (1397 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the
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The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid were validated by HPLC chromatography. Among the various extracts, the fruit extracts of A. senticosus and A. koreanum exhibited strongest antioxidant activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH radical scavenging activity was observed from the leaf extract of A. senticosus. In addition, the antioxidant activities of various extracts were correlated with total phenolic and proanthocyanidin contents. The major phenolic contents from various parts of these plants observed that leaf extract of A. senticosus expressed higher levels of chlorogenic acid (14.86 mg/dry weigh g) and caffeic acid (3.09 mg/dry weigh g) than other parts. Therefore, these results suggest that the leaf of A. senticosus may be an excellent natural source for functional foods and pharmaceutical agents, and the validated method was useful for the quality control of A. senticosus. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Extractions of Oil from Descurainia sophia Seed Using Supercritical CO2, Chemical Compositions by GC-MS and Evaluation of the Anti-Tussive, Expectorant and Anti-Asthmatic Activities
Molecules 2015, 20(7), 13296-13312; doi:10.3390/molecules200713296
Received: 19 May 2015 / Revised: 13 July 2015 / Accepted: 13 July 2015 / Published: 22 July 2015
Cited by 4 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text
Abstract
Descurainia sophia is widely distributed in China and is one of the most troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant oil, making it an important oil plant in China. The main goal of this study was to obtain
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Descurainia sophia is widely distributed in China and is one of the most troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant oil, making it an important oil plant in China. The main goal of this study was to obtain the maximum yield of the oil by an optimal selection of supercritical fluid extraction parameters. According to the central composite design and response surface methodology for supercritical fluid extraction method, a quadratic polynomial model was used to predict the yield of D. sophia seed oil. A series of runs was performed to assess the optimal extraction conditions. The results indicated that the extraction pressure had the greatest impact on oil yield within the range of the operating conditions studied. A total of approximately 67 compounds were separated in D. sophia seed oil by GC-MS, of which 51 compounds represented 98.21% of the total oils, for the first time. This study was also aimed at evaluating the anti-asthmatic, anti-tussive and expectorant activities in vivo of D. sophia seed oil which supplied for further research on bioactive constituents and pharmacological mechanisms. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Bioactive Cembranoids from the South China Sea Soft Coral Sarcophyton elegans
Molecules 2015, 20(7), 13324-13335; doi:10.3390/molecules200713324
Received: 13 June 2015 / Accepted: 13 July 2015 / Published: 22 July 2015
Cited by 5 | PDF Full-text (1130 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new cembranoids, sarcophelegans A–D (14) and six known analogues (510) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were elucidated through detailed spectroscopic analysis, and the absolute configuration
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Four new cembranoids, sarcophelegans A–D (14) and six known analogues (510) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were elucidated through detailed spectroscopic analysis, and the absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The antimigratory potential of compounds 110 were evaluated and compounds 2 and 6 were found to inhibit human breast tumor MDA-MB-231 cell migration at 10 μM. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Iminoiodane- and Brønsted Base-Mediated Cross Dehydrogenative Coupling of Cyclic Ethers with 1,3-Dicarbonyl Compounds
Molecules 2015, 20(7), 13336-13353; doi:10.3390/molecules200713336
Received: 1 June 2015 / Revised: 13 July 2015 / Accepted: 14 July 2015 / Published: 22 July 2015
Cited by 4 | PDF Full-text (1074 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-pot, two-step approach to prepare 2-tetrahydrofuran and -pyran substituted 1,3-dicarbonyl compounds by PhI=NTs-mediated amination/Brønsted base-catalyzed cross dehydrogenative coupling (CDC) reaction of the cyclic ether and 1,3-dicarbonyl derivative under mild conditions is reported. The reaction is compatible with a variety of cyclic ethers
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A one-pot, two-step approach to prepare 2-tetrahydrofuran and -pyran substituted 1,3-dicarbonyl compounds by PhI=NTs-mediated amination/Brønsted base-catalyzed cross dehydrogenative coupling (CDC) reaction of the cyclic ether and 1,3-dicarbonyl derivative under mild conditions is reported. The reaction is compatible with a variety of cyclic ethers and 1,3-dicarbonyl compounds, affording the corresponding coupled products in moderate to good yields of up to 80% over two steps. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Modeling the Photocatalytic Mineralization in Water of Commercial Formulation of Estrogens 17-β Estradiol (E2) and Nomegestrol Acetate in Contraceptive Pills in a Solar Powered Compound Parabolic Collector
Molecules 2015, 20(7), 13354-13373; doi:10.3390/molecules200713354
Received: 16 April 2015 / Revised: 13 June 2015 / Accepted: 6 July 2015 / Published: 22 July 2015
Cited by 4 | PDF Full-text (1514 KB) | HTML Full-text | XML Full-text
Abstract
Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove
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Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove commercial estradiol formulations (17-β estradiol and nomegestrol acetate) from water. Photolysis alone degraded up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm of TOC as initial concentration of the commercial estradiols formulation. The adsorption of estrogens over the catalyst was insignificant and was modeled by the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was modeled considering the reactor fluid-dynamics, the radiation field, the estrogens mass balance, and a modified Langmuir–Hinshelwood rate law, that was expressed in terms of the rate of photon adsorption. The optimum removal of the estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm diameter tubular CPC reactors which approached the optimum catalyst concentration and optical thickness determined from the modeling of the absorption of solar radiation in the CPC, by the six-flux absorption-scattering model (SFM). Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessArticle In Vivo Antihyperglycemic Activity of a Lanosteryl Triterpene from Protorhus longifolia
Molecules 2015, 20(7), 13374-13383; doi:10.3390/molecules200713374
Received: 27 May 2015 / Revised: 27 June 2015 / Accepted: 30 June 2015 / Published: 22 July 2015
Cited by 7 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text
Abstract
Control of postprandial hyperglycemia is crucial in the management of diabetes mellitus. Despite the use of the current hypoglycemic drugs, incidence of diabetes and related diseases continue to increase. This study aimed at evaluating the in vivo antihyperglycemic activity of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3
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Control of postprandial hyperglycemia is crucial in the management of diabetes mellitus. Despite the use of the current hypoglycemic drugs, incidence of diabetes and related diseases continue to increase. This study aimed at evaluating the in vivo antihyperglycemic activity of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), a lanosteryl triterpene isolated, and characterized from Protorhus longifolia stem bark. Spectroscopic data analysis was used to establish and verify the structure of the triterpene. The antihyperglycemic activity of the triterpene was evaluated in an STZ-induced diabetes rat model. The experimental animals were orally administered with RA-3 (100 mg/kg body weight) daily for 14 days. An oral glucose tolerance test was also performed. The animals were euthanized and biochemical analysis of antioxidant status, some glycolytic enzymes and glycogen content were conducted on serum and liver samples, respectively. RA-3 exhibited hypoglycemic activity by reducing blood glucose levels by 37%. The triterpene also improved glucose tolerance in the diabetic rats. Relatively higher hepatic glycogen content, hexokinase and glucokinase activity with a decrease in glucose-6-phosphatase activity were observed in the triterpene-treated diabetic group when compared with the diabetic control group. The triterpene treatment further increased antioxidant status of the diabetic animals; increased activity of superoxide dismutase and catalase were observed along with a decrease in malondialdehyde content. The results indicate potential pharmaceutical effects of lanosteryl triterpene in the management of diabetes mellitus. Full article
(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview The Emergence of Quinone Methides in Asymmetric Organocatalysis
Molecules 2015, 20(7), 11733-11764; doi:10.3390/molecules200711733
Received: 9 June 2015 / Revised: 17 June 2015 / Accepted: 19 June 2015 / Published: 25 June 2015
Cited by 64 | PDF Full-text (1491 KB) | HTML Full-text | XML Full-text
Abstract
Quinone methides (QMs) are highly reactive compounds that have been defined as “elusive” intermediates, or even as a “synthetic enigma” in organic chemistry. Indeed, there were just a handful of examples of their utilization in catalytic asymmetric settings until some years ago. This
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Quinone methides (QMs) are highly reactive compounds that have been defined as “elusive” intermediates, or even as a “synthetic enigma” in organic chemistry. Indeed, there were just a handful of examples of their utilization in catalytic asymmetric settings until some years ago. This review collects organocatalytic asymmetric reactions that employ QMs as substrates and intermediates, from the early examples, mostly based on stabilized QMs bearing specific substitution patterns, to more recent contributions, which have dramatically expanded the scope of QM chemistry. In fact, it was only very recently that the generation of QMs in situ through strategies compatible with organocatalytic methodologies has been realized. This tactic has finally opened the gate to the full exploitation of these unstable intermediates, leading to a series of remarkable disclosures. Several types of synthetically powerful asymmetric addition and cycloaddition reactions, applicable to a broad range of QMs, are now available. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessReview A Highlight of Recent Advances in Aptamer Technology and Its Application
Molecules 2015, 20(7), 11959-11980; doi:10.3390/molecules200711959
Received: 8 June 2015 / Revised: 23 June 2015 / Accepted: 25 June 2015 / Published: 30 June 2015
Cited by 49 | PDF Full-text (1254 KB) | HTML Full-text | XML Full-text
Abstract
Aptamers and SELEX (systematic evolution of ligands by exponential enrichment) technology have gained increasing attention over the past 25 years. Despite their functional similarity to protein antibodies, oligonucleotide aptamers have many unique properties that are suitable for clinical applications and industrialization. Aptamers may
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Aptamers and SELEX (systematic evolution of ligands by exponential enrichment) technology have gained increasing attention over the past 25 years. Despite their functional similarity to protein antibodies, oligonucleotide aptamers have many unique properties that are suitable for clinical applications and industrialization. Aptamers may be superior to antibodies in fields such as biomarker discovery, in vitro and in vivo diagnosis, precisely controlled drug release, and targeted therapy. However, aptamer commercialization has not occurred as quickly as expected, and few aptamer-based products have yet successfully entered clinical and industrial use. Thus, it is important to critically review some technical barriers of aptamer and SELEX technology per se that may impede aptamer development and application. To date, how to rapidly obtain aptamers with superior bioavailability over antibodies remains the key issue. In this review, we discuss different chemical and structural modification strategies aimed to enhance aptamer bioavailability. We also discuss improvements to SELEX process steps to shorten the selection period and improve the SELEX process success rate. Applications in which aptamers are particularly suited and perform differently or superior to antibodies are briefly introduced. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
Open AccessReview Analysis and Ranking of Protein-Protein Docking Models Using Inter-Residue Contacts and Inter-Molecular Contact Maps
Molecules 2015, 20(7), 12045-12060; doi:10.3390/molecules200712045
Received: 1 April 2015 / Revised: 8 June 2015 / Accepted: 17 June 2015 / Published: 1 July 2015
Cited by 3 | PDF Full-text (2813 KB) | HTML Full-text | XML Full-text
Abstract
In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available,
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In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessReview Light-Induced Infrared Difference Spectroscopy in the Investigation of Light Harvesting Complexes
Molecules 2015, 20(7), 12229-12249; doi:10.3390/molecules200712229
Received: 4 May 2015 / Revised: 16 June 2015 / Accepted: 17 June 2015 / Published: 3 July 2015
Cited by 4 | PDF Full-text (1659 KB) | HTML Full-text | XML Full-text
Abstract
Light-induced infrared difference spectroscopy (IR-DS) has been used, especially in the last decade, to investigate early photophysics, energy transfer and photoprotection mechanisms in isolated and membrane-bound light harvesting complexes (LHCs). The technique has the definite advantage to give information on how the pigments
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Light-induced infrared difference spectroscopy (IR-DS) has been used, especially in the last decade, to investigate early photophysics, energy transfer and photoprotection mechanisms in isolated and membrane-bound light harvesting complexes (LHCs). The technique has the definite advantage to give information on how the pigments and the other constituents of the biological system (proteins, membranes, etc.) evolve during a given photoreaction. Different static and time-resolved approaches have been used. Compared to the application of IR-DS to photosynthetic Reaction Centers (RCs), however, IR-DS applied to LHCs is still in an almost pioneering age: very often sophisticated techniques (step-scan FTIR, ultrafast IR) or data analysis strategies (global analysis, target analysis, multivariate curve resolution) are needed. In addition, band assignment is usually more complicated than in RCs. The results obtained on the studied systems (chromatophores and RC-LHC supercomplexes from purple bacteria; Peridinin-Chlorophyll-a-Proteins from dinoflagellates; isolated LHCII from plants; thylakoids; Orange Carotenoid Protein from cyanobacteria) are summarized. A description of the different IR-DS techniques used is also provided, and the most stimulating perspectives are also described. Especially if used synergically with other biophysical techniques, light-induced IR-DS represents an important tool in the investigation of photophysical/photochemical reactions in LHCs and LHC-containing systems. Full article
(This article belongs to the Special Issue Light-Harvesting Complexes)
Open AccessReview Relationship of Structure and Function of DNA-Binding Domain in Vitamin D Receptor
Molecules 2015, 20(7), 12389-12399; doi:10.3390/molecules200712389
Received: 28 May 2015 / Revised: 19 June 2015 / Accepted: 19 June 2015 / Published: 7 July 2015
Cited by 5 | PDF Full-text (1439 KB) | HTML Full-text | XML Full-text
Abstract
While the structure of the DNA-binding domain (DBD) of the vitamin D receptor (VDR) has been determined in great detail, the roles of its domains and how to bind the motif of its target genes are still under debate. The VDR DBD consists
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While the structure of the DNA-binding domain (DBD) of the vitamin D receptor (VDR) has been determined in great detail, the roles of its domains and how to bind the motif of its target genes are still under debate. The VDR DBD consists of two zinc finger modules and a C-terminal extension (CTE), at the end of the C-terminal of each structure presenting α-helix. For the first zinc finger structure, N37 and S-box take part in forming a dimer with 9-cis retinoid X receptor (RXR), while V26, R50, P-box and S-box participate in binding with VDR response elements (VDRE). For the second zinc finger structure, P61, F62 and H75 are essential in the structure of the VDR homodimer with the residues N37, E92 and F93 of the downstream of partner VDR, which form the inter-DBD interface. T-box of the CTE, especially the F93 and I94, plays a critical role in heterodimerization and heterodimers–VDRE binding. Six essential residues (R102, K103, M106, I107, K109, and R110) of the CTE α-helix of VDR construct one interaction face, which packs against the DBD core of the adjacent symmetry mate. In 1,25(OH)2D3-activated signaling, the VDR-RXR heterodimer may bind to DR3-type VDRE and ER9-type VDREs of its target gene directly resulting in transactivation and also bind to DR3-liked nVDRE of its target gene directly resulting in transrepression. Except for this, 1α,25(OH)2D3 ligand VDR-RXR may bind to 1αnVDRE indirectly through VDIR, resulting in transrepression of the target gene. Upon binding of 1α,25(OH)2D3, VDR can transactivate and transrepress its target genes depending on the DNA motif that DBD binds. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessReview Synthesis of Oxygen Heterocycles via Aromatic C-O Bond Formation Using Arynes
Molecules 2015, 20(7), 12558-12575; doi:10.3390/molecules200712558
Received: 17 June 2015 / Revised: 7 July 2015 / Accepted: 8 July 2015 / Published: 9 July 2015
Cited by 19 | PDF Full-text (1072 KB) | HTML Full-text | XML Full-text
Abstract
Most of the synthetic approaches to the benzo-fused heterocycles containing an oxygen atom have involved the use of phenol derivatives as a starting material. This review highlights the new synthetic approaches involving the aromatic C-O bond-forming process using arynes. The insertion of arynes
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Most of the synthetic approaches to the benzo-fused heterocycles containing an oxygen atom have involved the use of phenol derivatives as a starting material. This review highlights the new synthetic approaches involving the aromatic C-O bond-forming process using arynes. The insertion of arynes into the C=O bond gives the unstable intermediates, [2 + 2] cycloaddition-type adducts, which can be easily converted into a variety of oxygen atom-containing heterocycles in a single operation. In this review, the syntheses of oxygen heterocycles, such as coumarin, chromene, xanthene, dihydrobenzofuran and benzofuran derivatives, via the insertion of arynes into the C=O bond of aldehydes or formamides are summarized. Full article
(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)
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Open AccessReview Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids
Molecules 2015, 20(7), 12623-12651; doi:10.3390/molecules200712623
Received: 29 May 2015 / Revised: 6 July 2015 / Accepted: 7 July 2015 / Published: 13 July 2015
Cited by 4 | PDF Full-text (1550 KB) | HTML Full-text | XML Full-text
Abstract
HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV
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HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibition data for the strand transfer (ST) step are compared with in vitro anti-HIV data. The review also examines the issue of the lack of correlation between the ST enzymology data and anti-HIV assay results. Because this disconnect appeared to be a problem associated with permeability, prodrugs of these inhibitors were designed and synthesized. Prodrugs dramatically improved the anti-HIV activity data. For example, for compound, 96, the anti-HIV activity (EC50) improved from 500 nM for this diketo acid to 9 nM for its prodrug 116. In addition, there was excellent correlation between the IC50 and IC90 ST enzymology data for 96 (6 nM and 97 nM, respectively) and the EC50 and EC90 anti-HIV data for its prodrug 116 (9 nM and 94 nM, respectively). Finally, it was confirmed that the prodrug 116 was rapidly hydrolyzed in cells to the active compound 96. Full article
(This article belongs to the Special Issue Prodrugs)
Open AccessReview Tilting Plant Metabolism for Improved Metabolite Biosynthesis and Enhanced Human Benefit
Molecules 2015, 20(7), 12698-12731; doi:10.3390/molecules200712698
Received: 17 March 2015 / Revised: 29 April 2015 / Accepted: 12 May 2015 / Published: 13 July 2015
Cited by 6 | PDF Full-text (1559 KB) | HTML Full-text | XML Full-text
Abstract
The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this
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The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this biogenic pool of phytochemicals for products such as pharmaceuticals, fragrances, dyes, and insecticides, among others. With consumers showing increasing interests in these products, innovative biotechnological techniques are being developed and employed to alter plant secondary metabolism in efforts to improve on the quality and quantity of specific metabolites of interest. This review provides an overview of the biosynthesis for phytochemical compounds with medicinal and other related properties and their associated biological activities. It also provides an insight into how their biosynthesis/biosynthetic pathways have been modified/altered to enhance production. Full article
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Open AccessReview Metal- and Semimetal-Containing Inhibitors of Thioredoxin Reductase as Anticancer Agents
Molecules 2015, 20(7), 12732-12756; doi:10.3390/molecules200712732
Received: 1 April 2015 / Revised: 18 June 2015 / Accepted: 8 July 2015 / Published: 14 July 2015
Cited by 10 | PDF Full-text (1952 KB) | HTML Full-text | XML Full-text
Abstract
The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox homeostasis and signaling pathways. Recently, these selenoproteins have emerged as promising therapeutic targets for anticancer drug development, often being overexpressed in tumor
[...] Read more.
The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox homeostasis and signaling pathways. Recently, these selenoproteins have emerged as promising therapeutic targets for anticancer drug development, often being overexpressed in tumor cells and contributing to drug resistance. Herein, we summarize the current knowledge on metal- and semimetal-containing molecules capable of hampering mammalian TrxRs, with an emphasis on compounds reported in the last decade. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
Open AccessReview Recent Advances in the Synthesis of Carotenoid-Derived Flavours and Fragrances
Molecules 2015, 20(7), 12817-12840; doi:10.3390/molecules200712817
Received: 14 May 2015 / Revised: 2 July 2015 / Accepted: 8 July 2015 / Published: 15 July 2015
Cited by 4 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text
Abstract
Carotenoids are important isoprenoid compounds whose oxidative degradation produces a plethora of smaller derivatives, called apocarotenoids, which possess a range of different chemical structures and biological activities. Among these natural products, compounds having less than 15 carbon atoms in their frameworks are often
[...] Read more.
Carotenoids are important isoprenoid compounds whose oxidative degradation produces a plethora of smaller derivatives, called apocarotenoids, which possess a range of different chemical structures and biological activities. Among these natural products, compounds having less than 15 carbon atoms in their frameworks are often relevant flavours or fragrances and their manufacturing represents an important economic resource for chemical companies. The strict correlation between stereochemical structure and odour has made the stereospecific synthesis of the latter biological active compounds increasingly important. In this review, the recent advances on the synthesis of the most relevant carotenoid-derived flavours and fragrances are discussed. In particular, the new synthetic methods that have given new and innovative perspectives from a scientific standpoint and the preparative approaches that might possess industrial importance are described thoroughly. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessReview 68Ga-Based Radiopharmaceuticals: Production and Application Relationship
Molecules 2015, 20(7), 12913-12943; doi:10.3390/molecules200712913
Received: 7 June 2015 / Revised: 25 June 2015 / Accepted: 6 July 2015 / Published: 16 July 2015
Cited by 24 | PDF Full-text (5371 KB) | HTML Full-text | XML Full-text
Abstract
The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET) for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This
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The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET) for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessReview Carrier Modulation Layer-Enhanced Organic Light-Emitting Diodes
Molecules 2015, 20(7), 13005-13030; doi:10.3390/molecules200713005
Received: 30 May 2015 / Revised: 7 July 2015 / Accepted: 9 July 2015 / Published: 17 July 2015
Cited by 10 | PDF Full-text (2687 KB) | HTML Full-text | XML Full-text
Abstract
Organic light-emitting diode (OLED)-based display products have already emerged in the market and their efficiencies and lifetimes are sound at the comparatively low required luminance. To realize OLED for lighting application sooner, higher light quality and better power efficiency at elevated luminance are
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Organic light-emitting diode (OLED)-based display products have already emerged in the market and their efficiencies and lifetimes are sound at the comparatively low required luminance. To realize OLED for lighting application sooner, higher light quality and better power efficiency at elevated luminance are still demanded. This review reveals the advantages of incorporating a nano-scale carrier modulation layer (CML), also known as a spacer, carrier-regulating layer, or interlayer, among other terms, to tune the chromaticity and color temperature as well as to markedly improve the device efficiency and color rendering index (CRI) for numerous OLED devices. The functions of the CML can be enhanced as multiple layers and blend structures are employed. At proper thickness, the employment of CML enables the device to balance the distribution of carriers in the two emissive zones and achieve high device efficiencies and long operational lifetime while maintaining very high CRI. Moreover, we have also reviewed the effect of using CML on the most significant characteristics of OLEDs, namely: efficiency, luminance, life-time, CRI, SRI, chromaticity, and the color temperature, and see how the thickness tuning and selection of proper CML are crucial to effectively control the OLED device performance. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessReview Cell-Type Specific Penetrating Peptides: Therapeutic Promises and Challenges
Molecules 2015, 20(7), 13055-13070; doi:10.3390/molecules200713055
Received: 3 June 2015 / Revised: 19 June 2015 / Accepted: 10 July 2015 / Published: 20 July 2015
Cited by 15 | PDF Full-text (722 KB) | HTML Full-text | XML Full-text
Abstract
Cell penetrating peptides (CPP), also known as protein transduction domains (PTD), are small peptides able to carry peptides, proteins, nucleic acid, and nanoparticles, including viral particles, across the cellular membranes into cells, resulting in internalization of the intact cargo. In general, CPPs can
[...] Read more.
Cell penetrating peptides (CPP), also known as protein transduction domains (PTD), are small peptides able to carry peptides, proteins, nucleic acid, and nanoparticles, including viral particles, across the cellular membranes into cells, resulting in internalization of the intact cargo. In general, CPPs can be broadly classified into tissue-specific and non-tissue specific peptides, with the latter further sub-divided into three types: (1) cationic peptides of 6–12 amino acids in length comprised predominantly of arginine, lysine and/or ornithine residues; (2) hydrophobic peptides such as leader sequences of secreted growth factors or cytokines; and (3) amphipathic peptides obtained by linking hydrophobic peptides to nuclear localizing signals. Tissue-specific peptides are usually identified by screening of large peptide phage display libraries. These transduction peptides have the potential for a myriad of diagnostic as well as therapeutic applications, ranging from delivery of fluorescent or radioactive compounds for imaging, to delivery of peptides and proteins of therapeutic potential, and improving uptake of DNA, RNA, siRNA and even viral particles. Here we review the potential applications as well as hurdles to the tremendous potential of these CPPs, in particular the cell-type specific peptides. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
Open AccessReview Allergenic Proteins in Enology: A Review on Technological Applications and Safety Aspects
Molecules 2015, 20(7), 13144-13164; doi:10.3390/molecules200713144
Received: 9 March 2015 / Revised: 9 July 2015 / Accepted: 13 July 2015 / Published: 21 July 2015
Cited by 6 | PDF Full-text (713 KB) | HTML Full-text | XML Full-text
Abstract
Proteinaceous products are widely used as fining agents during winemaking to remove unwanted insoluble particles and undissolved microscopic particles (colloidal material) from the must or wine to improve stability. Some of them (egg white, caseinates, and fish gelatine) have allergenic potential and the
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Proteinaceous products are widely used as fining agents during winemaking to remove unwanted insoluble particles and undissolved microscopic particles (colloidal material) from the must or wine to improve stability. Some of them (egg white, caseinates, and fish gelatine) have allergenic potential and the presence of their residues in the final product could represent a risk for allergic individuals. Moreover, lysozyme (an egg allergen) is included among wine additives to control the fermentation processes and avoid spoiling during winemaking. The aim of this paper is to review the experimental/clinical data on the use of allergenic products in enology and the measurement of relative risk for sensitized subjects. In addition, methods developed specifically for the quantification of allergenic residues in must and wine are described. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessReview Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
Molecules 2015, 20(7), 13313-13323; doi:10.3390/molecules200713313
Received: 28 April 2015 / Revised: 10 June 2015 / Accepted: 9 July 2015 / Published: 22 July 2015
Cited by 15 | PDF Full-text (1290 KB) | HTML Full-text | XML Full-text
Abstract
In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface and subsequently endocytosed or actually transported into
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In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface and subsequently endocytosed or actually transported into the cytosol, either by direct plasma membrane penetration or after endocytosis. This discussion includes comments about pitfalls when using pharmacological inhibitors in such studies. The possibility of exploiting CPPs as carriers for the delivery of drugs of different sizes in vitro is discussed, as is the use of CPPs as carriers for therapeutic drugs or contrast agents in vivo. We conclude that in many cases, more studies are needed to demonstrate conclusively whether increased delivery of a substance attached to CPPs is due to a membrane-penetrating property or whether the increase is a consequence of just changing the charge of the substance to be delivered. Finally, the expected dose needed for the use of such conjugates in vivo is discussed, including aspects to consider in order to bring potential products into clinical use. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
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Open AccessReview Molecular Docking and Structure-Based Drug Design Strategies
Molecules 2015, 20(7), 13384-13421; doi:10.3390/molecules200713384
Received: 13 May 2015 / Revised: 14 July 2015 / Accepted: 20 July 2015 / Published: 22 July 2015
Cited by 66 | PDF Full-text (4565 KB) | HTML Full-text | XML Full-text
Abstract
Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of
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Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessReview Secondary Metabolites from Rubiaceae Species
Molecules 2015, 20(7), 13422-13495; doi:10.3390/molecules200713422
Received: 13 June 2015 / Revised: 11 July 2015 / Accepted: 13 July 2015 / Published: 22 July 2015
Cited by 10 | PDF Full-text (1216 KB) | HTML Full-text | XML Full-text
Abstract
This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids,
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This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion. Full article
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