Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Molecules, Volume 22, Issue 10 (October 2017)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-185
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Open AccessFeature PaperEditorial Special Issue: Sulfonamides
Molecules 2017, 22(10), 1642; doi:10.3390/molecules22101642
Received: 28 September 2017 / Accepted: 29 September 2017 / Published: 29 September 2017
PDF Full-text (170 KB) | HTML Full-text | XML Full-text
Abstract
The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a
[...] Read more.
The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively) [...] Full article
(This article belongs to the Special Issue Sulfonamides)
Open AccessFeature PaperEditorial Special Issue “Synthesis and Applications of Oligonucleotide Conjugates”
Molecules 2017, 22(10), 1700; doi:10.3390/molecules22101700
Received: 9 October 2017 / Revised: 10 October 2017 / Accepted: 11 October 2017 / Published: 13 October 2017
PDF Full-text (150 KB) | HTML Full-text | XML Full-text
Abstract
The underlying idea of oligonucleotide conjugates is to provide oligonucleotide with some novel property [...] Full article
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
Open AccessEditorial Special Issue: Improvements for Resveratrol Efficacy
Molecules 2017, 22(10), 1737; doi:10.3390/molecules22101737
Received: 10 October 2017 / Accepted: 11 October 2017 / Published: 16 October 2017
PDF Full-text (169 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a well-known phenolic stilbene because of its presence in several edible plants and its proposed properties that are beneficial to human health [...]
Full article
(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

Research

Jump to: Editorial, Review, Other

Open AccessArticle In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2
Molecules 2017, 22(10), 1484; doi:10.3390/molecules22101484
Received: 26 July 2017 / Accepted: 3 September 2017 / Published: 29 September 2017
PDF Full-text (3287 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here,
[...] Read more.
ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, we investigated the effect of six antiepileptic drugs (AEDs) viz. phenytoin, carbamazepine, valproate, lamotrigine, topiramate and levetiracetam, on the expression and function of ABCB1, ABCC1, ABCC2 and ABCG2 in Caco2 and HepG2 cell lines through real time PCR, western blot and functional activity assays. Further, the interaction of AEDs with maximally induced ABCC2 was studied. Carbamazepine caused a significant induction in expression of ABCB1 and ABCC2 in HepG2 and Caco2 cells, both at the transcript and protein level, together with increased functional activity. Valproate caused a significant increase in the expression and functional activity of ABCB1 in HepG2 only. No significant effect of phenytoin, lamotrigine, topiramate and levetiracetam on the transporters under study was observed in either of the cell lines. We demonstrated the interaction of carbamazepine and valproate with ABCC2 with ATPase and 5,6-carboxyfluorescein inhibition assays. Thus, altered functionality of ABCB1 and ABCC2 can affect the disposition and bioavailability of administered drugs, interfering with AED therapy. Full article
Figures

Figure 1

Open AccessArticle Immobilization of Moniliella spathulata R25L270 Lipase on Ionic, Hydrophobic and Covalent Supports: Functional Properties and Hydrolysis of Sardine Oil
Molecules 2017, 22(10), 1508; doi:10.3390/molecules22101508
Received: 13 August 2017 / Revised: 27 August 2017 / Accepted: 4 September 2017 / Published: 25 September 2017
PDF Full-text (820 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The oleaginous yeast Moniliella spathulata R25L270 was the first yeast able to grow and produce extracellular lipase using Macaúba (Acrocomia aculeate) cake as substrate. The novel lipase was recently identified, and presented promising features for biotechnological applications. The M. spathulata R25L270
[...] Read more.
The oleaginous yeast Moniliella spathulata R25L270 was the first yeast able to grow and produce extracellular lipase using Macaúba (Acrocomia aculeate) cake as substrate. The novel lipase was recently identified, and presented promising features for biotechnological applications. The M. spathulata R25L270 lipase efficiently hydrolyzed vegetable and animal oils, and showed selectivity for generating cis-5,8,11,15,17-eicosapentaenoic acid from sardine oil. The enzyme can act in a wide range of temperatures (25–48 °C) and pH (6.5–8.4). The present study deals with the immobilization of M. spathulata R25L270 lipase on hydrophobic, covalent and ionic supports to select the most active biocatalyst capable to obtain omega-3 fatty acids (PUFA) from sardine oil. Nine immobilized agarose derivatives were prepared and biochemically characterized for thermostability, pH stability and catalytic properties (KM and Vmax). Ionic supports improved the enzyme–substrate affinity; however, it was not an effective strategy to increase the M. spathulata R25L270 lipase stability against pH and temperature. Covalent support resulted in a biocatalyst with decreased activity, but high thermostability. The enzyme was most stabilized when immobilized on hydrophobic supports, especially Octyl-Sepharose. Compared with the free enzyme, the half-life of the Octyl-Sepharose derivative at 60 °C increased 10-fold, and lipase stability under acidic conditions was achieved. The Octyl-Sepharose derivative was selected to obtain omega-3 fatty acids from sardine oil, and the maximal enzyme selectivity was achieved at pH 5.0. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
Figures

Figure 1

Open AccessArticle Antimicrobial Effects of Violacein against Planktonic Cells and Biofilms of Staphylococcus aureus
Molecules 2017, 22(10), 1534; doi:10.3390/molecules22101534
Received: 7 August 2017 / Revised: 7 September 2017 / Accepted: 9 September 2017 / Published: 25 September 2017
PDF Full-text (1021 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Violacein is an indole compound, produced by Chromobacterium violaceum, a bacteria present in tropical and subtropical areas. Among its numerous biological activities, its antimicrobial potential stands out. This study aims to determine the antimicrobial activity of VIO on S. aureus in planktonic
[...] Read more.
Violacein is an indole compound, produced by Chromobacterium violaceum, a bacteria present in tropical and subtropical areas. Among its numerous biological activities, its antimicrobial potential stands out. This study aims to determine the antimicrobial activity of VIO on S. aureus in planktonic culture and biofilms. VIO showed excellent antimicrobial activity in inhibiting and killing S. aureus in planktonic cultures and biofilm formation. The minimum bactericidal concentration (5 μg/mL) of VIO caused the death of S. aureus after 3–4 h of exposure and the minimum inhibitory concentration (1.25 μg/mL) of VIO inhibited bacterial growth within the first 8 h of contact. Biofilm formation was also strongly inhibited by VIO (1.25 μg/mL), in contrast to the higher resistance verified for S. aureus in mature biofilm (40 μg/mL). The high bacterial metabolic activity favored VIO activity; however, the good activity observed during phases of reduced metabolism indicates that VIO action involves more than one mechanism. Thus, VIO is a promising molecule for the development of an antimicrobial drug for the eradication of S. aureus infections. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
Figures

Figure 1

Open AccessArticle Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide
Molecules 2017, 22(10), 1560; doi:10.3390/molecules22101560
Received: 26 August 2017 / Revised: 8 September 2017 / Accepted: 13 September 2017 / Published: 12 October 2017
Cited by 1 | PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients’ noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century
[...] Read more.
Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients’ noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB. Full article
(This article belongs to the collection Nanomedicine)
Figures

Figure 1

Open AccessArticle Cytotoxic and Hypoglycemic Activity of Triterpenoid Saponins from Camellia oleifera Abel. Seed Pomace
Molecules 2017, 22(10), 1562; doi:10.3390/molecules22101562
Received: 19 July 2017 / Revised: 14 September 2017 / Accepted: 15 September 2017 / Published: 21 September 2017
PDF Full-text (1108 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A3, oleiferasaponin A1, camelliasaponin B1, and camelliasaponin B2. The structure
[...] Read more.
One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A3, oleiferasaponin A1, camelliasaponin B1, and camelliasaponin B2. The structure of oleiferasaponin A3 was elucidated as 16α-hydroxy-21β-O-angeloyl-22α-O-cinnamoyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-xylopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-gluco-pyranosiduronic acid. Camelliasaponin B1 and camelliasaponin B2 exhibited potent cytotoxic activity on three human tumour cell lines (human lung tumour cells (A549), human liver tumour cells (HepG2), cervical tumour cells (Hela)). The hypoglycemic activity of oleiferasaponin A1 was testified by protecting pancreatic β-cell lines from high-glucose damage. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Figure 1

Open AccessArticle Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure
Molecules 2017, 22(10), 1574; doi:10.3390/molecules22101574
Received: 21 August 2017 / Accepted: 16 September 2017 / Published: 25 September 2017
PDF Full-text (3639 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using
[...] Read more.
Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Figure 1

Open AccessArticle N-Halamine Biocidal Materials with Superior Antimicrobial Efficacies for Wound Dressings
Molecules 2017, 22(10), 1582; doi:10.3390/molecules22101582
Received: 21 August 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 21 September 2017
PDF Full-text (1249 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This work demonstrated the successful application of N-halamine technology for wound dressings rendered antimicrobial by facile and inexpensive processes. Four N-halamine compounds, which possess different functional groups and chemistry, were synthesized. The N-halamine compounds, which contained oxidative chlorine, the source of antimicrobial activity,
[...] Read more.
This work demonstrated the successful application of N-halamine technology for wound dressings rendered antimicrobial by facile and inexpensive processes. Four N-halamine compounds, which possess different functional groups and chemistry, were synthesized. The N-halamine compounds, which contained oxidative chlorine, the source of antimicrobial activity, were impregnated into or coated onto standard non-antimicrobial wound dressings. N-halamine-employed wound dressings inactivated about 6 to 7 logs of Staphylococcus aureus and Pseudomonas aeruginosa bacteria in brief periods of contact time. Moreover, the N-halamine-modified wound dressings showed superior antimicrobial efficacies when compared to commercially available silver wound dressings. Zone of inhibition tests revealed that there was no significant leaching of the oxidative chlorine from the materials, and inactivation of bacteria occurred by direct contact. Shelf life stability tests showed that the dressings were stable to loss of oxidative chlorine when they were stored for 6 months in dark environmental conditions. They also remained stable under florescent lighting for up to 2 months of storage. They could be stored in opaque packaging to improve their shelf life stabilities. In vitro skin irritation testing was performed using a three-dimensional human reconstructed tissue model (EpiDerm™). No potential skin irritation was observed. In vitro cytocompatibility was also evaluated. These results indicate that N-halamine wound dressings potentially can be employed to prevent infections, while at the same time improving the healing process by eliminating undesired bacterial growth. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
Figures

Figure 1

Open AccessCommunication Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells
Molecules 2017, 22(10), 1583; doi:10.3390/molecules22101583
Received: 25 August 2017 / Revised: 20 September 2017 / Accepted: 20 September 2017 / Published: 21 September 2017
PDF Full-text (1259 KB) | HTML Full-text | XML Full-text
Abstract
The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7
[...] Read more.
The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (13), a sesquiterpene (4), two steroids (56), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 13 had IC50 values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds 13 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 13 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 13 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 13 could be promising lead compounds for the development of novel anti-inflammatory agents. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle The Recognition of Calmodulin to the Target Sequence of Calcineurin—A Novel Binding Mode
Molecules 2017, 22(10), 1584; doi:10.3390/molecules22101584
Received: 15 August 2017 / Revised: 18 September 2017 / Accepted: 18 September 2017 / Published: 21 September 2017
PDF Full-text (6055 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Calcineurin (CaN) is a Ca2+/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in
[...] Read more.
Calcineurin (CaN) is a Ca2+/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in the presence of minimal levels of Ca2+, but the enzyme is inactive until activated by CaM. Upon binding to CaM, CaN then undergoes a conformational rearrangement, the auto inhibitory domain is displaced and thus allows for full activity. In order to elucidate the regulatory role of CaM in the activation processes of CaN, we used NMR spectroscopy to determine the structure of the complex of CaM and the target peptide of CaN (CaNp). The CaM/CaNp complex shows a compact ellipsoidal shape with 8 α-helices of CaM wrapping around the CaNp helix. The RMSD of backbone and heavy atoms of twenty lowest energy structures of CaM/CaNp complex are 0.66 and 1.14 Å, respectively. The structure of CaM/CaNp complex can be classified as a novel binding mode family 1–18 with major anchor residues Ile396 and Leu413 to allocate the largest space between two domains of CaM. The relative orientation of CaNp to CaM is similar to the CaMKK peptide in the 1–16 binding mode with N- and C-terminal hydrophobic anchors of target sequence engulfed in the hydrophobic pockets of the N- and C-domain of CaM, respectively. In the light of the structural model of CaM/CaNp complex reported here, we provide new insight in the activation processes of CaN by CaM. We propose that the hydrophobic interactions between the Ca2+-saturated C-domain and C-terminal half of the target sequence provide driving forces for the initial recognition. Subsequent folding in the target sequence and structural readjustments in CaM enhance the formation of the complex and affinity to calcium. The electrostatic repulsion between CaM/CaNp complex and AID may result in the displacement of AID from active site for full activity. Full article
(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)
Figures

Figure 1

Open AccessArticle Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao
Molecules 2017, 22(10), 1587; doi:10.3390/molecules22101587
Received: 19 August 2017 / Revised: 14 September 2017 / Accepted: 19 September 2017 / Published: 21 September 2017
PDF Full-text (5047 KB) | HTML Full-text | XML Full-text
Abstract
Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and
[...] Read more.
Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and deapio-platycodin D, two main components in Jiegeng. However, whether Jiegeng could alter the pharmacokinetics of the main compounds in Gancao is still unknown. Thus, the purpose of this study was to compare the oral pharmacokinetics of flavonoids and saponins from Gancao alone vs. after co-administration with Jiegeng. Furthermore, Caco-2 cell transport and fecal hydrolysis were investigated to explain the altered pharmacokinetic properties. Pharmacokinetics results suggested that the bioavailability of liquiritin, isoliquiritin, glycyrrhizin and its metabolite, glycyrrhetinic acid, could be improved while bioavailability of liquiritigenin and isoliquiritigenin deteriorated when co-administered with Jiegeng. The Caco-2 transport study showed no significant difference of the Papp values of the main components in Jiegeng Gancao decoction when compared with those in Gancao decoction (p > 0.05). The in vitro metabolism study suggested that saponins and flavonoids glycosides in Gancao were influenced and the metabolic characteristics of most ingredients were consistent with pharmacokinetic results, such as liquiritin and glycyrrhetinic acid. The hydrolysis of liquiritigenin and glycyrrhizin observed with fecal lysate in vitro appeared consistent with the oral pharmacokinetics. Based on experiments, the pharmacokinetic profiles of six components in Gancao were influenced by Jiegeng. The metabolic process might partially contribute to the altered pharmacokinetic behavior. The metabolism of some components of Gancao appeared to be inhibited when coadministered with Jiegeng, possibly by the Jiegeng constituent platycodin. Full article
Figures

Figure 1

Open AccessArticle Novel FXa Inhibitor Identification through Integration of Ligand- and Structure-Based Approaches
Molecules 2017, 22(10), 1588; doi:10.3390/molecules22101588
Received: 28 August 2017 / Revised: 15 September 2017 / Accepted: 18 September 2017 / Published: 22 September 2017
PDF Full-text (7314 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and
[...] Read more.
Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and electrostatic similarity search and protein-ligand docking to discover novel FXa-targeted scaffolds for further development of inhibitors. From an initial set of 260,000 compounds from the NCI Open database, 30 potential FXa inhibitors were identified and selected for in vitro biological evaluation. Compound 5 (NSC635393, 4-(3-methyl-4H-1,4-benzothiazin-2-yl)-2,4-dioxo-N-phenylbutanamide) displayed an IC50 value of 2.02 nM against human FXa. The identified compound may serve as starting point for the development of novel FXa inhibitors. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling
Molecules 2017, 22(10), 1589; doi:10.3390/molecules22101589
Received: 24 August 2017 / Revised: 18 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
PDF Full-text (3117 KB) | HTML Full-text | XML Full-text
Abstract
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62
[...] Read more.
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra) or 0.2 µM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity. Full article
Figures

Open AccessArticle Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes
Molecules 2017, 22(10), 1590; doi:10.3390/molecules22101590
Received: 2 August 2017 / Accepted: 13 September 2017 / Published: 21 September 2017
PDF Full-text (1194 KB) | HTML Full-text | XML Full-text
Abstract
Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide
[...] Read more.
Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated. In this study, we investigated the drug interaction potential of two selaginellins on ten P450 isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and 3A) and six UGT isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using human liver microsomes and liquid chromatography-tandem mass spectrometry. Selaginellin and selaginellin M had high inhibitory potential for CYP2C8-mediated amodiaquine O-demethylation with IC50 values of 0.5 and 0.9 μM, respectively. Selaginellin and selaginellin M also showed medium inhibitory potential against CYP2C9, CYP2J2, UGT1A1, and UGT1A3 (1 μM < IC50 < 5 μM). These two selaginellins had low inhibitory potential against CYP1A2, CYP2A6, CYP2E1, and UGT1A6 (IC50 > 25 μM). This information might be helpful to predict possible drug interaction potential of between selaginellins and co-administered drugs. Full article
Figures

Figure 1

Open AccessFeature PaperArticle One-Pot Multi-Enzymatic Synthesis of the Four Stereoisomers of 4-Methylheptan-3-ol
Molecules 2017, 22(10), 1591; doi:10.3390/molecules22101591
Received: 24 July 2017 / Revised: 12 September 2017 / Accepted: 21 September 2017 / Published: 22 September 2017
PDF Full-text (756 KB) | HTML Full-text | XML Full-text
Abstract
The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible
[...] Read more.
The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible stereoisomers of this compound were prepared from 4-methylhept-4-en-3-one by a one-pot procedure in which the two stereogenic centres were created during two sequential reductions catalysed by an ene-reductase (ER) and an alcohol dehydrogenase (ADH), respectively. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Figures

Open AccessArticle Synthesis of 2,4-Diaminopyrimidine Core-Based Derivatives and Biological Evaluation of Their Anti-Tubercular Activities
Molecules 2017, 22(10), 1592; doi:10.3390/molecules22101592
Received: 4 September 2017 / Revised: 19 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
PDF Full-text (2679 KB) | HTML Full-text | XML Full-text
Abstract
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site,
[...] Read more.
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice
Molecules 2017, 22(10), 1593; doi:10.3390/molecules22101593
Received: 30 July 2017 / Revised: 9 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
PDF Full-text (2908 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO)
[...] Read more.
Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Open AccessArticle Therapeutic Mechanisms of Vernonia amygdalina Delile in the Treatment of Prostate Cancer
Molecules 2017, 22(10), 1594; doi:10.3390/molecules22101594
Received: 28 August 2017 / Revised: 19 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
PDF Full-text (1788 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the
[...] Read more.
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases. However, to the best of our knowledge, no previous reports have explored its therapeutic efficacy against human prostate cancer. The objective of the present study was to assess the anticancer activities of VAD methanolic extracts in the prevention and treatment of prostate cancer using human androgen-independent prostate cancer (PC-3) cells as a test model. To achieve our objective, PC-3 cells were treated with various doses of VAD for 48 h. Data generated from the trypan blue test and MTT assay demonstrated that VAD extracts exhibited significant growth-inhibitory effects on PC-3 cells. Collectively, we established for the first time the antiproliferative effects of VAD on PC-3 cells, with an IC50 value of about 196.6 µg/mL. Further experiments, including cell morphology, lipid peroxidation and comet assays, and apoptosis analysis showed that VAD caused growth-inhibitory effects on PC-3 cells through the induction of cell growth arrest, DNA damage, apoptosis, and necrosis in vitro and may provide protection from oxidative stress diseases as a result of its high antioxidant content. These results provide useful data on the anticancer activities of VAD for prostate cancer and demonstrate the novel possibilities of this medicinal plant for developing prostate cancer therapies. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Figure 1

Open AccessArticle Antifungal Activity of Thapsia villosa Essential Oil against Candida, Cryptococcus, Malassezia, Aspergillus and Dermatophyte Species
Molecules 2017, 22(10), 1595; doi:10.3390/molecules22101595
Received: 31 July 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
PDF Full-text (446 KB) | HTML Full-text | XML Full-text
Abstract
The composition of the essential oil (EO) of Thapsia villosa (Apiaceae), isolated by hydrodistillation from the plant’s aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5%) and methyleugenol (35.9%), were evaluated against clinically
[...] Read more.
The composition of the essential oil (EO) of Thapsia villosa (Apiaceae), isolated by hydrodistillation from the plant’s aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5%) and methyleugenol (35.9%), were evaluated against clinically relevant yeasts (Candida spp., Cryptococcus neoformans and Malassezia furfur) and moulds (Aspergillus spp. and dermatophytes). Minimum inhibitory concentrations (MICs) were measured according to the broth macrodilution protocols by Clinical and Laboratory Standards Institute (CLSI). The EO, limonene and methyleugenol displayed low MIC and MFC (minimum fungicidal concentration) values against Candida spp., Cryptococcus neoformans, dermatophytes, and Aspergillus spp. Regarding Candida species, an inhibition of yeast–mycelium transition was demonstrated at sub-inhibitory concentrations of the EO (MIC/128; 0.01 μL/mL) and their major compounds in Candida albicans. Fluconazole does not show this activity, and the combination with low concentrations of EO could associate a supplementary target for the antifungal activity. The association of fluconazole with T. villosa oil does not show antagonism, but the combination limonene/fluconazole displays synergism. The fungistatic and fungicidal activities revealed by T. villosa EO and its main compounds, associated with their low haemolytic activity, confirm their potential antimicrobial interest against fungal species often associated with human mycoses. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe)
Figures

Figure 1

Open AccessArticle Separation and Enrichment of Lectin from Zihua Snap-Bean (Phaseolus vulgaris) Seeds by PEG 600–Ammonium Sulfate Aqueous Two-Phase System
Molecules 2017, 22(10), 1596; doi:10.3390/molecules22101596
Received: 7 September 2017 / Revised: 18 September 2017 / Accepted: 21 September 2017 / Published: 22 September 2017
PDF Full-text (2263 KB) | HTML Full-text | XML Full-text
Abstract
A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH4)2SO4 aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box–Behnken design (BBD), involving four factors at
[...] Read more.
A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH4)2SO4 aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box–Behnken design (BBD), involving four factors at three levels each subjected to analysis of variance (ANOVA) and response surface analysis, the protein recovery and the purification factor of lectin in the top phase were used as the response values of the variance analysis to acquire the multivariate quadratic regression model. SDS–PAGE electrophoresis and the hemagglutination test were used to detect the distribution of lectin in the aqueous two-phase system (ATPS). The obtained data indicated that lectin was preferentially partitioned into the PEG-rich phase, and the ATPS, composed of 15% (NH4)2SO4 (w/w), 18% PEG 600 (w/w), 0.4 g/5 g NaCl and 1 mL crude extract, showed good selectivity for lectin when the pH value was 7.5. Under the optimal conditions, most of the lectin was assigned to the top phase in the ATPS, and the hemagglutination activity of the purified lectin in the top phase was 3.08 times that of the crude extract. Consequently, the PEG 600/(NH4)2SO4 aqueous two-phase system was an effective method for separating and enriching lectin directly from the crude extract of Zihua snap-bean seeds. Full article
Figures

Open AccessArticle Biomimetic-Functionalized, Tannic Acid-Templated Mesoporous Silica as a New Support for Immobilization of NHase
Molecules 2017, 22(10), 1597; doi:10.3390/molecules22101597
Received: 23 August 2017 / Revised: 18 September 2017 / Accepted: 19 September 2017 / Published: 25 September 2017
PDF Full-text (2889 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission
[...] Read more.
Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), and Fourier transform infrared (FT-IR) and the results showed that the Dop-TAMS possessed sufficiently large pore size and volume for the accommodation of NHase. Studying the thermal stability, storage, shaking stability, and pH stability of the free and immobilized NHase indicated that the catalytic properties of NHase@Dop-TAMS were significantly enhanced. Moreover, the NHase@Dop-TAMS exhibited good reusability. All the results demonstrated that Dop-TAMS could be used as an excellent matrix for the immobilization of NHase. Full article
(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)
Figures

Open AccessArticle Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery
Molecules 2017, 22(10), 1598; doi:10.3390/molecules22101598
Received: 12 August 2017 / Revised: 7 September 2017 / Accepted: 17 September 2017 / Published: 24 September 2017
PDF Full-text (3218 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by
[...] Read more.
Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
Figures

Figure 1

Open AccessArticle Integrative Pathway Analysis of Genes and Metabolites Reveals Metabolism Abnormal Subpathway Regions and Modules in Esophageal Squamous Cell Carcinoma
Molecules 2017, 22(10), 1599; doi:10.3390/molecules22101599
Received: 22 August 2017 / Revised: 20 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
PDF Full-text (2928 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aberrant metabolism is one of the main driving forces in the initiation and development of ESCC. Both genes and metabolites play important roles in metabolic pathways. Integrative pathway analysis of both genes and metabolites will thus help to interpret the underlying biological phenomena.
[...] Read more.
Aberrant metabolism is one of the main driving forces in the initiation and development of ESCC. Both genes and metabolites play important roles in metabolic pathways. Integrative pathway analysis of both genes and metabolites will thus help to interpret the underlying biological phenomena. Here, we performed integrative pathway analysis of gene and metabolite profiles by analyzing six gene expression profiles and seven metabolite profiles of ESCC. Multiple known and novel subpathways associated with ESCC, such as ‘beta-Alanine metabolism’, were identified via the cooperative use of differential genes, differential metabolites, and their positional importance information in pathways. Furthermore, a global ESCC-Related Metabolic (ERM) network was constructed and 31 modules were identified on the basis of clustering analysis in the ERM network. We found that the three modules located just to the center regions of the ERM network—especially the core region of Module_1—primarily consisted of aldehyde dehydrogenase (ALDH) superfamily members, which contributes to the development of ESCC. For Module_4, pyruvate and the genes and metabolites in its adjacent region were clustered together, and formed a core region within the module. Several prognostic genes, including GPT, ALDH1B1, ABAT, WBSCR22 and MDH1, appeared in the three center modules of the network, suggesting that they can become potentially prognostic markers in ESCC. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Open AccessArticle Hydrogen-Bonding Interactions in Luminescent Quinoline-Triazoles with Dominant 1D Crystals
Molecules 2017, 22(10), 1600; doi:10.3390/molecules22101600
Received: 24 August 2017 / Revised: 14 September 2017 / Accepted: 15 September 2017 / Published: 22 September 2017
PDF Full-text (3524 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal
[...] Read more.
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal direction of growth. Crystals of 13 are 1D tape and prism shapes that correlate with their intermolecular and solvent 1D lattice H-bonding interactions. All compounds were thermally stable up to about 200 C and blue-green emissive in solution. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Solvent-Free Synthesis and Safener Activity of Sulfonylurea Benzothiazolines
Molecules 2017, 22(10), 1601; doi:10.3390/molecules22101601
Received: 19 August 2017 / Revised: 21 September 2017 / Accepted: 21 September 2017 / Published: 22 September 2017
PDF Full-text (2566 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel sulfonylurea benzothiazolines was designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological
[...] Read more.
A series of novel sulfonylurea benzothiazolines was designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorsulfuron to bind with the herbicide target enzyme active site to attain detoxification. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle Identification of DNA-Binding Proteins Using Mixed Feature Representation Methods
Molecules 2017, 22(10), 1602; doi:10.3390/molecules22101602
Received: 15 August 2017 / Revised: 19 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
PDF Full-text (807 KB) | HTML Full-text | XML Full-text
Abstract
DNA-binding proteins play vital roles in cellular processes, such as DNA packaging, replication, transcription, regulation, and other DNA-associated activities. The current main prediction method is based on machine learning, and its accuracy mainly depends on the features extraction method. Therefore, using an efficient
[...] Read more.
DNA-binding proteins play vital roles in cellular processes, such as DNA packaging, replication, transcription, regulation, and other DNA-associated activities. The current main prediction method is based on machine learning, and its accuracy mainly depends on the features extraction method. Therefore, using an efficient feature representation method is important to enhance the classification accuracy. However, existing feature representation methods cannot efficiently distinguish DNA-binding proteins from non-DNA-binding proteins. In this paper, a multi-feature representation method, which combines three feature representation methods, namely, K-Skip-N-Grams, Information theory, and Sequential and structural features (SSF), is used to represent the protein sequences and improve feature representation ability. In addition, the classifier is a support vector machine. The mixed-feature representation method is evaluated using 10-fold cross-validation and a test set. Feature vectors, which are obtained from a combination of three feature extractions, show the best performance in 10-fold cross-validation both under non-dimensional reduction and dimensional reduction by max-relevance-max-distance. Moreover, the reduced mixed feature method performs better than the non-reduced mixed feature technique. The feature vectors, which are a combination of SSF and K-Skip-N-Grams, show the best performance in the test set. Among these methods, mixed features exhibit superiority over the single features. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Figure 1

Open AccessArticle Influence of Harvest Season and Cultivar on the Variation of Phenolic Compounds Composition and Antioxidant Properties in Vaccinium ashei Leaves
Molecules 2017, 22(10), 1603; doi:10.3390/molecules22101603
Received: 20 August 2017 / Revised: 14 September 2017 / Accepted: 20 September 2017 / Published: 30 September 2017
PDF Full-text (695 KB) | HTML Full-text | XML Full-text
Abstract
The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were
[...] Read more.
The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were Aliceblue, Powderblue, Climax, Bluegem and FloridaM. It was observed that leaves from March had the highest TPC values (222 ± 1 mg gallic acid equivalents/g to Aliceblue cultivar) and highest TFC values (49.8 ± 0.8 and 48.7 ± 0.7 µg rutin/g to Clímax and Powderblue cultivars, respectively). The chromatographic profile was quantitatively similar, however, the proportions of each compound were influenced by cultivar and harvest season. Chlorogenic acid and rutin were the main identified phenolic compounds, but chlorogenic acid was the most abundant in both harvest seasons. Antioxidant capacities values ranged from 5.80 ± 0.04 to 105 ± 2 µg/mL (DPPH) and 178 ± 5 to 431 ± 8 mmol Trolox/100 g (ORAC). The cultivar Bluegem by March had the highest values in both assays. The results indicate that the blueberry leaves from different cultivars and harvest seasons have different phenolic compounds content and different antioxidant capacities. In addition, the antioxidant properties demonstrated a high correlation with rutin content. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1
Molecules 2017, 22(10), 1604; doi:10.3390/molecules22101604
Received: 22 August 2017 / Revised: 21 September 2017 / Accepted: 21 September 2017 / Published: 24 September 2017
PDF Full-text (2215 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone
[...] Read more.
Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-formyl umbelliferone (2), from Angelica decursiva, and the synthesis of 8-formyl umbelliferone (3) from 1. We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure–activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1, respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD. Full article
(This article belongs to the Special Issue Versatile Coumarins)
Figures

Figure 1

Open AccessArticle Evaluation of LPS-Induced Acute Lung Injury Attenuation in Rats by Aminothiazole-Paeonol Derivatives
Molecules 2017, 22(10), 1605; doi:10.3390/molecules22101605
Received: 1 September 2017 / Revised: 20 September 2017 / Accepted: 21 September 2017 / Published: 25 September 2017
PDF Full-text (2754 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells
[...] Read more.
Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents. Full article
(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)
Figures

Open AccessArticle Small Molecules Derived from Thieno[3,4-c]pyrrole-4,6-dione (TPD) and Their Use in Solution Processed Organic Solar Cells
Molecules 2017, 22(10), 1607; doi:10.3390/molecules22101607
Received: 18 August 2017 / Revised: 14 September 2017 / Accepted: 22 September 2017 / Published: 30 September 2017
PDF Full-text (2779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work, microwave synthesis, chemical, optical and electrochemical characterization of three small organic molecules, TPA-TPD, TPA-PT-TPD and TPA-TT-TPD with donor-acceptor structure and their use in organic photovoltaic cells are reported. For the synthesis, 5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione was
[...] Read more.
In this work, microwave synthesis, chemical, optical and electrochemical characterization of three small organic molecules, TPA-TPD, TPA-PT-TPD and TPA-TT-TPD with donor-acceptor structure and their use in organic photovoltaic cells are reported. For the synthesis, 5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione was used as electron withdrawing fragment while the triphenylamine was used as electron donating fragment. Molecular electronic geometry and electronic distribution density were established by density functional theory (DFT) calculations and confirmed by optical and chemical characterization. These molecules were employed as electron-donors in the active layer for manufacturing bulk heterojunction organic solar cells, where [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) was used as electron-acceptor. As cathode, Field′s metal (FM), an eutectic alloy (Bi/In/Sn: 32.5%, 51%, and 16.5%, respectively) with a melting point above 62 °C, was easily deposited by drop casting under vacuum-free process and at air atmosphere. Prepared devices based on TPA-TPD:PC71BM (1:4 w/w ratio) presented a large VOC = 0.97 V, with JSC = 7.9 mA/cm2, a FF = 0.34, then, a power conversion efficiency (PCE) of 2.6%. Full article
(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)
Figures

Open AccessArticle Identification of Carotenoids and Isoprenoid Quinones from Asaia lannensis and Asaia bogorensis
Molecules 2017, 22(10), 1608; doi:10.3390/molecules22101608
Received: 4 September 2017 / Revised: 24 September 2017 / Accepted: 24 September 2017 / Published: 25 September 2017
PDF Full-text (4901 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia, that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a
[...] Read more.
The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia, that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a laboratory liquid culture minimal medium with 2% sucrose. Carotenoids and isoprenoid quinones were investigated using UHPLC-DAD-ESI-MS analysis. In general, tested strains of Asaia spp. were able to produce 10 carotenoids and 3 isoprenoid quinones: menaquinone-7, menaquinone-8, and ubiquinone-10. The main identified carotenoids in Asaia lannensis strains were phytofluene, neurosporene, α-carotene, while for Asaia bogorensis, neurosporene, canthaxanthin, and zeaxanthin were noted. What is more, tested Asaia spp. were able to produce myxoxanthophyll, which has so far been identified primarily in cyanobacteria. The results show that A. lannensis are characterized by statistically higher concentrations of produced carotenoids, as well as a greater variety of these compounds. We have noted that carotenoids were not only accumulated by bacterial cells, but also some strains of A. lannensis produced extracellular carotenoids. Full article
(This article belongs to the Section Metabolites)
Figures

Figure 1

Open AccessFeature PaperArticle Comparison of Dilution, Filtration, and Microwave Digestion Sample Pretreatments in Elemental Profiling of Wine by ICP-MS
Molecules 2017, 22(10), 1609; doi:10.3390/molecules22101609
Received: 1 September 2017 / Accepted: 23 September 2017 / Published: 25 September 2017
PDF Full-text (1551 KB) | HTML Full-text | XML Full-text
Abstract
Wine elemental composition varies by cultivar, geographic origin, viticultural and enological practices, and is often used for authenticity validation. Elemental analysis of wine by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is challenging due to the potential for non-spectral interferences and plasma instability arising
[...] Read more.
Wine elemental composition varies by cultivar, geographic origin, viticultural and enological practices, and is often used for authenticity validation. Elemental analysis of wine by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is challenging due to the potential for non-spectral interferences and plasma instability arising from organic matrix components. Sample preparation mitigates these interferences, however, conflicting recommendations of best practices in ICP-MS analysis of wine have been reported. This study compared direct dilution, microwave-assisted acid digestion, and two filtration sample pretreatments, acidification prior to filtration and filtration followed by acidification, in elemental profiling of one white and three red table wines by ICP-MS. Of 43 monitored isotopes, 37 varied by sample preparation method, with significantly higher results of 17 isotopes in the microwave-digested samples. Both filtration treatments resulted in lower results for 11 isotopes compared to the other methods. Finally, isotope dilution determination of copper based on natural abundances and the 63Cu:65Cu instrument response ratio agreed with external calibration and confirmed a significant sample preparation effect. Overall, microwave digestion did not compare favorably, and direct dilution was found to provide the best compromise between ease of use and result accuracy and precision, although all preparation strategies were able to differentiate the wines. Full article
(This article belongs to the collection Wine Chemistry)
Figures

Figure 1

Open AccessArticle Astragalus Polysaccharide Protect against Cadmium-Induced Cytotoxicity through the MDA5/NF-κB Pathway in Chicken Peripheral Blood Lymphocytes
Molecules 2017, 22(10), 1610; doi:10.3390/molecules22101610
Received: 26 August 2017 / Revised: 20 September 2017 / Accepted: 22 September 2017 / Published: 25 September 2017
PDF Full-text (14941 KB) | HTML Full-text | XML Full-text
Abstract
Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS
[...] Read more.
Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the MDA5/NF-κB signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [NF-κB] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (MDA5), interferon promoter-stimulating factor 1 (IPS-1), NF-κB, and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of MDA5, IPS-1, NF-κB, and their downstream cytokines, IL-1β and TNF-α, IL-6 in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls (p < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the MDA5 signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling. Full article
(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)
Figures

Figure 1

Open AccessArticle Acyclic Triterpenoids from Alpinia katsumadai Inhibit IL-6-Induced STAT3 Activation
Molecules 2017, 22(10), 1611; doi:10.3390/molecules22101611
Received: 25 August 2017 / Accepted: 21 September 2017 / Published: 25 September 2017
PDF Full-text (1461 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The seeds of Alpinia katsumadai yielded two new acyclic triterpenoids, 2,3,6,22,23-pentahydroxy-2,6,11,15,19,23-hexamethyl-tetracosa-7,10,14,18-tetraene (3) and 2,3,6,22,23-pentahydroxy-2,10,15,19,23-hexamethyl-7-methylenetetracosa-10,14,18-triene (4), as well as two known compounds, 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (1) and 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (2). The absolute configurations of 2 and 3, which
[...] Read more.
The seeds of Alpinia katsumadai yielded two new acyclic triterpenoids, 2,3,6,22,23-pentahydroxy-2,6,11,15,19,23-hexamethyl-tetracosa-7,10,14,18-tetraene (3) and 2,3,6,22,23-pentahydroxy-2,10,15,19,23-hexamethyl-7-methylenetetracosa-10,14,18-triene (4), as well as two known compounds, 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (1) and 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (2). The absolute configurations of 2 and 3, which were determined by means of a modified Mosher’s method, are suggested as (3R; 5S; 22R) and (3R; 22R), respectively. Compounds 14 inhibited IL-6-induced JAK2/STAT3 activity in a dose-dependent fashion, with IC50 values of 0.67, 0.71, 2.18, and 2.99 μM. Moreover, IL-6-stimulated phosphorylation of STAT3 was significantly suppressed in U266 cells by the administration of A. katsumadai EtOH extract and Compounds 1 and 2. These results suggest that major phytochemicals, Compounds 1 and 2, obtained from A. katsumadai may be useful candidates for designing new IL-6 inhibitors as anti-inflammatory agents. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
Figures

Open AccessArticle Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk.) via 1H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models
Molecules 2017, 22(10), 1612; doi:10.3390/molecules22101612
Received: 17 August 2017 / Accepted: 21 September 2017 / Published: 25 September 2017
PDF Full-text (4714 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The
[...] Read more.
Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The current study addresses the chemical differences and similarities between gaharu samples of different grades, obtained commercially, using 1H-NMR-based metabolomics. Two classification models: partial least squares-discriminant analysis (PLS-DA) and Random Forests were developed to classify the gaharu samples on the basis of their chemical constituents. The gaharu samples could be reclassified into a ‘high grade’ group (samples A, B and D), characterized by high contents of kusunol, jinkohol, and 10-epi-γ-eudesmol; an ‘intermediate grade’ group (samples C, F and G), dominated by fatty acid and vanillic acid; and a ‘low grade’ group (sample E and H), which had higher contents of aquilarone derivatives and phenylethyl chromones. The results showed that 1H- NMR-based metabolomics can be a potential method to grade the quality of gaharu samples on the basis of their chemical constituents. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Figures

Open AccessArticle Efficacy of Bioactive Cyclic Peptides in Rheumatoid Arthritis: Translation from In Vitro to In Vivo Models
Molecules 2017, 22(10), 1613; doi:10.3390/molecules22101613
Received: 10 August 2017 / Accepted: 15 September 2017 / Published: 25 September 2017
PDF Full-text (6912 KB) | HTML Full-text | XML Full-text
Abstract
Using a novel drug discovery technology reported in previous issues of this journal cyclic peptides have been created which are able to down-regulate secretion of inflammatory cytokines, in vitro, by stimulated cells of the macrophage cell line J774. The cytokines in question,
[...] Read more.
Using a novel drug discovery technology reported in previous issues of this journal cyclic peptides have been created which are able to down-regulate secretion of inflammatory cytokines, in vitro, by stimulated cells of the macrophage cell line J774. The cytokines in question, TNF-alpha and IL-6, are strongly implicated in etiology of diseases such as rheumatoid arthritis. Studies are reported here using the CAIA animal model for rheumatoid arthritis, which show that the peptides identified are indeed able to impact on inflammation of joints, induced in vivo. The results suggest that these peptides are effective at a dose which could be viable in man, and at which no adverse side effects are evident in the short term. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
Figures

Figure 1

Open AccessArticle In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis
Molecules 2017, 22(10), 1614; doi:10.3390/molecules22101614
Received: 4 September 2017 / Revised: 20 September 2017 / Accepted: 21 September 2017 / Published: 26 September 2017
PDF Full-text (11398 KB) | HTML Full-text | XML Full-text
Abstract
Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that
[...] Read more.
Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression. Methods: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin. Results: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression. Conclusions: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle Solid-State Form Characterization of Riparin I
Molecules 2017, 22(10), 1615; doi:10.3390/molecules22101615
Received: 27 August 2017 / Accepted: 22 September 2017 / Published: 9 October 2017
PDF Full-text (5747 KB) | HTML Full-text | XML Full-text
Abstract
Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5),
[...] Read more.
Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5), obtained by the same synthesis process, were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), DSC-photovisual, Thermogravimetry (TG), Fourier Transform Infrared (FTIR), Pyrolysis (Pyr-GC/MS), X-ray Powder Diffraction (PXRD), and Solid-State Nuclear Magnetic Resonance (ssNMR) techniques. Batches of riparin I with different crystal habits resulting in crystallization impurities were observed, which can be attributed to the presence of triethylamine. The main differences were observed by DSC, PXRD, and ssNMR analysis. DSC curves of RIP-2 and RIP-3 presented endothermic peaks at different temperatures of fusion, which can be attributed to the mixture of different crystalline forms. PXRD and ssNMR results confirmed crystallinity differences. The results offer evidence of the importance of controlling the reproducibility of the synthesis in order to obtain the adequate morphology for therapeutic efficacy and avoiding future problems in quality control of riparin I products. Full article
Figures

Figure 1

Open AccessArticle Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent
Molecules 2017, 22(10), 1616; doi:10.3390/molecules22101616
Received: 3 September 2017 / Revised: 20 September 2017 / Accepted: 21 September 2017 / Published: 26 September 2017
PDF Full-text (1470 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on
[...] Read more.
In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ–A (40–1000 mg/kg). The prolonged t1/2 and greater area under concentration-time curve (AUC) versus time (AUC0–t) of DNJ for SZ–A than for purified DNJ has been observed after both oral and intravenous administration. It was found that other components in SZ–A could enhance the absorption of DNJ through the intestinal barrier. The major distribution tissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were mainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was revealed to be partly due to the biotransformation of other components in SZ–A via gut microbiota. These information provide a rational basis for the use of SZ–A in clinical practice. Full article
Figures

Figure 1

Open AccessArticle A Network Pharmacology-Based Study on the Hepatoprotective Effect of Fructus Schisandrae
Molecules 2017, 22(10), 1617; doi:10.3390/molecules22101617
Received: 17 August 2017 / Accepted: 17 September 2017 / Published: 28 September 2017
PDF Full-text (814 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried
[...] Read more.
Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the hepatoprotective mechanism of Wuweizi as an effective therapeutic approach to treat liver disease. Multiple active compounds of Wuweizi were docked with 44 protein targets related with viral hepatitis, fatty liver, liver fibrosis, cirrhosis, and liver cancer. A compound–target network was constructed through network pharmacology analysis, predicting the relationships of active ingredients to the targets. Our results demonstrated that schisantherin, schisandrin B, schisandrol B, kadsurin, Wuweizisu C, Gomisin A, Gomisin G, and angeloylgomisin may target with 21 intracellular proteins associated with liver diseases, especially with fatty liver disease. The CYP2E1, PPARα, and AMPK genes and their related pathway may play a pivotal role in the hepatoprotective effects of Wuweizi. The network pharmacology strategy used provides a forceful tool for searching the action mechanism of traditional herbal medicines and novel bioactive ingredients. Full article
Figures

Figure 1

Open AccessArticle A Fluorescent Coumarin-Based Probe for the Fast Detection of Cysteine with Live Cell Application
Molecules 2017, 22(10), 1618; doi:10.3390/molecules22101618
Received: 23 August 2017 / Revised: 19 September 2017 / Accepted: 20 September 2017 / Published: 26 September 2017
PDF Full-text (3405 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new coumarin-based fluorescent probe, containing an allylic esters group, has been designed and synthesized for sensing cysteine in physiological pH. In this fluorescent probe, the coumarin was applied as the fluorophore and an allylic esters group was combined as both a fluorescence
[...] Read more.
A new coumarin-based fluorescent probe, containing an allylic esters group, has been designed and synthesized for sensing cysteine in physiological pH. In this fluorescent probe, the coumarin was applied as the fluorophore and an allylic esters group was combined as both a fluorescence quencher and a recognition unit. The probe can selectively and sensitively detect cysteine (Cys) over homocysteine, glutathione, and other amino acids, and has a rapid response time of 30 min and a low detection limit of 47.7 nM. In addition, the probe could be applied for cell imaging with low cytotoxicity. Full article
Figures

Open AccessArticle NMR Detection of Semi-Specific Antibody Interactions in Serum Environments
Molecules 2017, 22(10), 1619; doi:10.3390/molecules22101619
Received: 9 August 2017 / Accepted: 22 September 2017 / Published: 27 September 2017
PDF Full-text (2284 KB) | HTML Full-text | XML Full-text
Abstract
Although antibody functions are executed in heterogeneous blood streams characterized by molecular crowding and promiscuous intermolecular interaction, detailed structural characterizations of antibody interactions have thus far been performed under homogeneous in vitro conditions. NMR spectroscopy potentially has the ability to study protein structures
[...] Read more.
Although antibody functions are executed in heterogeneous blood streams characterized by molecular crowding and promiscuous intermolecular interaction, detailed structural characterizations of antibody interactions have thus far been performed under homogeneous in vitro conditions. NMR spectroscopy potentially has the ability to study protein structures in heterogeneous environments, assuming that the target protein can be labeled with NMR-active isotopes. Based on our successful development of isotope labeling of antibody glycoproteins, here we apply NMR spectroscopy to characterize antibody interactions in heterogeneous extracellular environments using mouse IgG-Fc as a test molecule. In human serum, many of the HSQC peaks originating from the Fc backbone exhibited attenuation in intensity of various magnitudes. Similar spectral changes were induced by the Fab fragment of polyclonal IgG isolated from the serum, but not by serum albumin, indicating that a subset of antibodies reactive with mouse IgG-Fc exists in human serum without preimmunization. The metaepitopes recognized by serum polyclonal IgG cover the entire molecular surface of Fc, including the binding sites to Fc receptors and C1q. In-serum NMR observation will offer useful tools for the detailed characterization of biopharamaceuticals, including therapeutic antibodies in physiologically relevant heterogeneous environments, also giving deeper insight into molecular recognition by polyclonal antibodies in the immune system. Full article
(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)
Figures

Figure 1

Open AccessArticle Time-Dependent Antimicrobial Activity of Filtering Nonwovens with Gemini Surfactant-Based Biocides
Molecules 2017, 22(10), 1620; doi:10.3390/molecules22101620
Received: 30 August 2017 / Accepted: 25 September 2017 / Published: 27 September 2017
PDF Full-text (1438 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies on nonwovens used for respiratory protective devices (RPDs) were related to equipment intended for short-term use. There is only limited research on the development of biocidal nonwoven fabrics for reusable RPDs that could be used safely in an industrial work environment
[...] Read more.
Previous studies on nonwovens used for respiratory protective devices (RPDs) were related to equipment intended for short-term use. There is only limited research on the development of biocidal nonwoven fabrics for reusable RPDs that could be used safely in an industrial work environment where there is a risk of microbial growth. Moreover, a new group of biocides with high antimicrobial activity—gemini surfactants, has never been explored for textile’s application in previous studies. The aim of this study was to develop high-efficiency melt-blown nonwovens containing gemini surfactants with time-dependent biocidal activity, and to validate their antimicrobial properties under conditions simulating their use at a plant biomass-processing unit. A set of porous biocidal structures (SPBS) was prepared and applied to the melt-blown polypropylene (PP) nonwovens. The biocidal properties of the structures were triggered by humidity and had different activation rates. Scanning electron microscopy was used to undertake structural studies of the modified PP/SPBS nonwovens. In addition, simulation of plant biomass dust deposition on the nonwovens was performed. The biocidal activity of PP/SPBS nonwovens was evaluated following incubation with Escherichia coli and Aspergillus niger from the American Type Culture Collection, and with Pseudomonas fluorescens and Penicillium chrysogenum isolated from the biomass. PP/SPBS nonwovens exhibited antimicrobial activity to varying levels. Higher antimicrobial activity was noted for bacteria (R = 87.85–97.46%) and lower for moulds (R = 80.11–94.53%). Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
Figures

Figure 1

Open AccessArticle DPPH Radical Scavenging and Postprandial Hyperglycemia Inhibition Activities and Flavonoid Composition Analysis of Hawk Tea by UPLC-DAD and UPLC-Q/TOF MSE
Molecules 2017, 22(10), 1622; doi:10.3390/molecules22101622
Received: 28 August 2017 / Accepted: 20 September 2017 / Published: 13 October 2017
PDF Full-text (1746 KB) | XML Full-text
Abstract
Hawk tea (Litsea coreana Lévl. var. Lanuginosa (Migo) Yen C. Yang & P.H. Huang), a very popular herbal tea material, has attracted more and more attention due to its high antioxidant properties and possible therapeutic effect on type II diabetes mellitus. The
[...] Read more.
Hawk tea (Litsea coreana Lévl. var. Lanuginosa (Migo) Yen C. Yang & P.H. Huang), a very popular herbal tea material, has attracted more and more attention due to its high antioxidant properties and possible therapeutic effect on type II diabetes mellitus. The raw materials of Hawk tea are usually divided into three kinds: bud tea (BT), primary leaf tea (PLT) and mature leaf tea (MLT). In this study, the DPPH radical scavenging activity and the antimicrobial properties of these three kinds of Hawk tea from different regions were comparatively investigated, and a ultra-high performance liquid chromatographic coupled with a photodiode array detector (UPLC-DAD) method was employed for comparison of the three major flavonoid constituents, including hyperoside, isoquercitrin and astragalin, in different samples of Hawk tea. At the same time, the effect of methanol extract (ME) of PLT on the mouse postprandial blood glucose and the effect of ME and its different fractions (petroleum ether fraction (PE), ethyl acetate fraction (EA), n-butanol fraction (n-BuOH), and water fraction (WF)) on the activity of α-glucosidase were studied. The results showed that Hawk BT and Hawk PLT possessed the higher radicals scavenging activity than Hawk MLT, while the antibacterial activity against P. vulgaris of PLT and MLT was higher than Hawk BT. The contents of the three major flavonoid constituents in samples of Hawk PLT are higher than Hawk BT and Hawk MLT. The mouse postprandial blood glucose levels of the middle dose (0.5 g/kg) group and the high dose (1 g/kg) group with oral administration of the ME of PLT were significantly lower than the control group. What’s more, the inhibitory effect of ME of PLT and its EA and n-BuOH fractions on α-glucosidase was significantly higher than that of acarbose. Rapid ultra-high performance liquid chromatography/quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was used to identify the flavonoids in Hawk PLT, and a total of 20 flavonoids were identified or tentatively identified by comparing their retention times and accurate mass measurements with reference compounds or literature data. The bioactive flavonoid composition and DPPH radical scavenging activities present in different Hawk tea raw materials are quite different due to the different ontogenesis of these raw materials. Further studies on PLT showed that the substances in PLT ME could reduce the level of mouse postprandial blood glucose through inhibiting the activity of α-glucosidase. Full article
Open AccessArticle Effect of Cadmium and Copper Exposure on Growth, Secondary Metabolites and Antioxidant Activity in the Medicinal Plant Sambung Nyawa (Gynura procumbens (Lour.) Merr)
Molecules 2017, 22(10), 1623; doi:10.3390/molecules22101623
Received: 4 September 2017 / Revised: 21 September 2017 / Accepted: 26 September 2017 / Published: 12 October 2017
PDF Full-text (774 KB) | HTML Full-text | XML Full-text
Abstract
A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no
[...] Read more.
A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no Cd and Cu); (2) Cd 2 = cadmium 2 mg/L; (3) Cd 4 = cadmium 4 mg/L; (4) Cu 70 = copper 70 mg/L; (5) Cu 140 = copper 140 mg/L); (6) Cd 2 + Cu 70 = cadmium 2 mg/L + copper 70 mg/L); (7) Cd 2 + Cu 140 = cadmium 2 mg/L + copper 70 mg/L); (8) Cd 4 + Cu 70 = cadmium 4 mg/L+ copper 70 mg/L and (9) Cd 4 + Cu 140 = cadmium 4 mg/L + copper 140 mg/L) were evaluated in this experiment. It was found that the growth parameters (plant dry weight, total leaf area and basal diameter) were reduced with the exposure to increased concentrations of Cd and Cu and further decreased under interaction between Cd and Cu. Production of total phenolics, flavonoids and saponin was observed to be reduced under combined Cd and Cu treatment. The reduction in the production of plant secondary metabolites might be due to lower phenyl alanine lyase (PAL) activity under these conditions. Due to that, the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and antibacterial activities was also found to be reduced by the combined treatments. The current experiments show that the medicinal properties of G. procumbens are reduced by cadmium and copper contamination. The accumulation of heavy metal also was found to be higher than the safety level recommended by the WHO in the single and combined treatments of Cd and Cu. These results indicate that exposure of G. procumbens to Cd and Cu contaminated soil may potentially harm consumers due to bioaccumulation of metals and reduced efficacy of the herbal product. Full article
Figures

Figure 1

Open AccessArticle Design, Synthesis, and Antitumor Activity of Novel Quinazoline Derivatives
Molecules 2017, 22(10), 1624; doi:10.3390/molecules22101624
Received: 28 August 2017 / Revised: 16 September 2017 / Accepted: 26 September 2017 / Published: 28 September 2017
PDF Full-text (1230 KB) | HTML Full-text | XML Full-text
Abstract
In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, 1H-NMR, 13C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on
[...] Read more.
In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, 1H-NMR, 13C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on stilbeneamino were detected. These synthesized compounds were evaluated for antitumor activity in vitro against eight human tumor cell lines with an MTS assay. Most synthesized compounds exhibited more potent activity (IC50 = ~2.0 μM) than gefitinib (IC50 > 10.0 μM) against the A431, A549, and BGC-823 cell lines. Docking methodology of compound 6c and 6i binding into the ATP site of EGFR was carried out. The results showed that fluorine and trifluoromethyl played an important role in efficient cell activity. Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Open AccessArticle Valorization of Lignin by Partial Wet Oxidation Using Sustainable Heteropoly Acid Catalysts
Molecules 2017, 22(10), 1625; doi:10.3390/molecules22101625
Received: 12 September 2017 / Revised: 25 September 2017 / Accepted: 27 September 2017 / Published: 28 September 2017
PDF Full-text (2138 KB) | HTML Full-text | XML Full-text
Abstract
The production of carboxylic acids by partial wet oxidation of alkali lignin at elevated temperatures and pressures was studied experimentally. Two different heteropoly acids, phosphotungstic acid (H3PW12O40) and phosphomolybdic acid (H3PMo12O40),
[...] Read more.
The production of carboxylic acids by partial wet oxidation of alkali lignin at elevated temperatures and pressures was studied experimentally. Two different heteropoly acids, phosphotungstic acid (H3PW12O40) and phosphomolybdic acid (H3PMo12O40), were used to catalyze the oxidation of lignin under hydrothermal conditions. Factors influencing the total yield of carboxylic acids formed during the partial oxidation of lignin were investigated. Formic, acetic and succinic acids were the major products identified. Of the two catalysts used, phosphomolybdic acid gave the most promising results, with carboxylic acid yields and lignin conversions of up to 45% and 95%, respectively. Full article
(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)
Figures

Open AccessArticle Anticarcinogenic Effect of Spices Due to Phenolic and Flavonoid Compounds—In Vitro Evaluation on Prostate Cells
Molecules 2017, 22(10), 1626; doi:10.3390/molecules22101626
Received: 2 September 2017 / Accepted: 24 September 2017 / Published: 28 September 2017
PDF Full-text (2938 KB) | Supplementary Files
Abstract
This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway
[...] Read more.
This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway seed extracts. The strongest inhibitory effect on prostatic cells was observed after the application of extracts of spices in concentration of 12.5 mg·mL−1. An LC/MS analysis identified that the most abundant phenolic and flavonoid compounds in black pepper are 3,4-dihydroxybenzaldehyde and naringenin chalcone, while the most abundant phenolic and flavonoid compounds in caraway seeds are neochlorogenic acid and apigenin. Using an MTT assay for the phenolic and flavonoid compounds from spices, we identified the IC50 value of ~1 mmol·L−1 PNT1A. The scratch test demonstrated that the most potent inhibitory effect on PNT1A, 22RV1 and PC3 cells is from the naringenin chalcone contained in black pepper. From the spectrum of compounds assessed, the naringenin chalcone contained in black pepper was identified as the most potent inhibitor of the growth of prostate cells. Full article
Figures

Open AccessArticle Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model
Molecules 2017, 22(10), 1627; doi:10.3390/molecules22101627
Received: 12 September 2017 / Revised: 23 September 2017 / Accepted: 27 September 2017 / Published: 29 September 2017
PDF Full-text (2387 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption
[...] Read more.
Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin (1), glycyrrhetic acid-3-O-mono-β-d-glucuronide (2), and glycyrrhetinic acid (3); and the selected major flavonoids, licochalcone A (4), licochalcone B (5), licochalcone C (6), echinatin (7), isoliquiritin apioside (8), liquiritigenin (9), liquiritin apioside (10) isolated from Glycyrrhizae radix et rhizoma, were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3, 57, and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1, 8, and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Figure 1

Open AccessArticle Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds
Molecules 2017, 22(10), 1628; doi:10.3390/molecules22101628
Received: 1 August 2017 / Revised: 22 September 2017 / Accepted: 24 September 2017 / Published: 28 September 2017
PDF Full-text (1070 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5aj were synthesized via one-pot, four-component condensation reactions of aryl aldehydes 1aj, propanedinitrile (2), hydrazine hydrate (3) and ethyl acetoacetate (4) under solvent-free conditions. We report
[...] Read more.
A series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5aj were synthesized via one-pot, four-component condensation reactions of aryl aldehydes 1aj, propanedinitrile (2), hydrazine hydrate (3) and ethyl acetoacetate (4) under solvent-free conditions. We report herein the use of the Brønsted acid ionic liquid (BAIL) triethylammonium hydrogen sulphate [Et3NH][HSO4] as catalyst for this multi-component synthesis. Compared with the available reaction methodology, this new method has consistent advantages, including excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. Selected synthesized derivatives were evaluated for in vitro anticancer activity against four human cancer cell lines viz. melanoma cancer cell line (SK-MEL-2), breast cancer cell line(MDA-MB-231), leukemia cancer cell line (K-562) and cervical cancer cell line (HeLa). Compounds 5b, 5d, 5g, 5h and 5j exhibited promising anticancer activity against all selected human cancer cell lines, except HeLa. Molecular docking studies also confirmed 5b and 5d as good lead molecules. An in silico ADMET study of the synthesized anticancer agents indicated good oral drug-like behavior and non-toxic nature. Full article
(This article belongs to the Special Issue ECSOC-20)
Figures

Open AccessArticle Predicting the Global Potential Distribution of Four Endangered Panax Species in Middle-and Low-Latitude Regions of China by the Geographic Information System for Global Medicinal Plants (GMPGIS)
Molecules 2017, 22(10), 1630; doi:10.3390/molecules22101630
Received: 21 August 2017 / Revised: 18 September 2017 / Accepted: 25 September 2017 / Published: 28 September 2017
PDF Full-text (9875 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Global biodiversity is strongly influenced by the decrease in endangered biological species. Predicting the distribution of endangered medicinal plants is necessary for resource conservation. A spatial distribution model—geographic information system for global medicinal plants (GMPGIS)—is used to predict the global potential suitable distribution
[...] Read more.
Global biodiversity is strongly influenced by the decrease in endangered biological species. Predicting the distribution of endangered medicinal plants is necessary for resource conservation. A spatial distribution model—geographic information system for global medicinal plants (GMPGIS)—is used to predict the global potential suitable distribution of four endangered Panax species, including Panax japonicas (T. Nees) C. A. Meyer and Panax japonicas var. major (Burkill) C. Y. Wu & K. M. Feng distributed in low- and middle-latitude, Panax zingiberensis C. Y. Wu & K. M. Feng and Panax stipuleanatus C. T. Tsai & K. M. Feng in low-latitude regions of China based on seven bioclimatic variables and 600 occurrence points. Results indicate that areas of P. japonicus and P. japonicus var. major are 266.29 × 105 and 77.5 × 105 km2, respectively, which are mainly distributed in China and America. By contrast, the areas of P. zingiberensis and P. stipuleanatus are 5.09 × 105 and 2.05 × 105 km2, respectively, which are mainly distributed in Brazil and China. P. japonicus has the widest distribution among the four species. The data also indicate that the mean temperature of coldest quarter is the most critical factor. This scientific prediction can be used as reference for resource conservation of endangered plants and as a guide to search for endangered species in previously unknown areas. Full article
Figures

Figure 1

Open AccessArticle Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone
Molecules 2017, 22(10), 1631; doi:10.3390/molecules22101631
Received: 12 September 2017 / Revised: 25 September 2017 / Accepted: 28 September 2017 / Published: 30 September 2017
PDF Full-text (1893 KB) | HTML Full-text | XML Full-text
Abstract
Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently,
[...] Read more.
Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320’s aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 μM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease. Full article
Figures

Figure 1

Open AccessCommunication Investigation of the N-Terminus Amino Function of Arg10-Teixobactin
Molecules 2017, 22(10), 1632; doi:10.3390/molecules22101632
Received: 28 August 2017 / Revised: 24 September 2017 / Accepted: 25 September 2017 / Published: 28 September 2017
PDF Full-text (712 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In
[...] Read more.
Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In this regard, a large number of analogs with substitutions in both the cycle and the tail has been described. Here, we report the contribution of the N-terminus residue, N-Me-d-Phe, to the activity of Arg10-teixobactin. On the basis of our findings, we conclude that the N-terminus accepts minimum changes but not the presence of long alkyl chains. The presence of a positive charge is a requirement for the activity of the peptide. Furthermore, acylation of the N-terminus leads to total loss of activity. Full article
(This article belongs to the Special Issue Peptide Therapeutics)
Figures

Open AccessArticle Profiles of Volatile Flavor Compounds in Milk Fermented with Different Proportional Combinations of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus
Molecules 2017, 22(10), 1633; doi:10.3390/molecules22101633
Received: 28 August 2017 / Revised: 19 September 2017 / Accepted: 28 September 2017 / Published: 29 September 2017
PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus are key factors in the fermentation process and the final quality of dairy products worldwide. This study was performed to investigate the effects of the proportions of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus isolated from
[...] Read more.
Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus are key factors in the fermentation process and the final quality of dairy products worldwide. This study was performed to investigate the effects of the proportions of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus isolated from traditionally fermented dairy products in China and Mongolia on the profile of volatile compounds produced in samples. Six proportional combinations (1:1, 1:10, 1:50, 1:100, 1:1000, and 1:10,000) of L. delbrueckii subsp. bulgaricus IMAU20401 to S. thermophilus ND03 were considered, and the volatiles were identified and quantified by solid-phase microextraction and gas chromatography–mass spectrometry (SPME-GC-MS) against an internal standard. In total, 89 volatile flavor compounds, consisting of aldehydes, ketones, acids, alcohols, esters, and aromatic hydrocarbons, were identified. Among these, some key flavor volatile compounds were identified, including acetaldehyde, 3-methylbutanal, acetoin, 2-heptanone, acetic acid, butanoic acid, and 3-methyl-1-butanol. The of L. delbrueckii subsp. bulgaricus IMAU20401 to S. thermophilus ND03 influenced the type and concentration of volatiles produced. In particular, aldehydes and ketones were present at higher concentrations in the 1:1000 treatment combination than in the other combinations. Our findings emphasize the importance of selecting the appropriate proportions of L. delbrueckii subsp. bulgaricus and S. thermophilus for the starter culture in determining the final profile of volatiles and the overall flavor of dairy products. Full article
Figures

Figure 1

Open AccessFeature PaperArticle Halogen Bonds Formed between Substituted Imidazoliums and N Bases of Varying N-Hybridization
Molecules 2017, 22(10), 1634; doi:10.3390/molecules22101634
Received: 28 August 2017 / Revised: 26 September 2017 / Accepted: 27 September 2017 / Published: 29 September 2017
PDF Full-text (789 KB) | HTML Full-text | XML Full-text
Abstract
Heterodimers are constructed containing imidazolium and its halogen-substituted derivatives as Lewis acid. N in its sp3, sp2 and sp hybridizations is taken as the electron-donating base. The halogen bond is strengthened in the Cl < Br < I order, with
[...] Read more.
Heterodimers are constructed containing imidazolium and its halogen-substituted derivatives as Lewis acid. N in its sp3, sp2 and sp hybridizations is taken as the electron-donating base. The halogen bond is strengthened in the Cl < Br < I order, with the H-bond generally similar in magnitude to the Br-bond. Methyl substitution on the N electron donor enhances the binding energy. Very little perturbation arises if the imidazolium is attached to a phenyl ring. The energetics are not sensitive to the hybridization of the N atom. More regular patterns appear in the individual phenomena. Charge transfer diminishes uniformly on going from amine to imine to nitrile, a pattern that is echoed by the elongation of the C-Z (Z=H, Cl, Br, I) bond in the Lewis acid. These trends are also evident in the Atoms in Molecules topography of the electron density. Molecular electrostatic potentials are not entirely consistent with energetics. Although I of the Lewis acid engages in a stronger bond than does H, it is the potential of the latter which is much more positive. The minimum on the potential of the base is most negative for the nitrile even though acetonitrile does not form the strongest bonds. Placing the systems in dichloromethane solvent reduces the binding energies but leaves intact most of the trends observed in vacuo; the same can be said of ∆G in solution. Full article
(This article belongs to the Special Issue Halogen Bonds and Beyond)
Figures

Figure 1

Open AccessArticle A New Series of Cytotoxic Pyrazoline Derivatives as Potential Anticancer Agents that Induce Cell Cycle Arrest and Apoptosis
Molecules 2017, 22(10), 1635; doi:10.3390/molecules22101635
Received: 12 September 2017 / Accepted: 26 September 2017 / Published: 29 September 2017
PDF Full-text (2562 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new series of pyrazoline derivatives 1b12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these
[...] Read more.
A new series of pyrazoline derivatives 1b12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these new derivatives, the compounds 3-(4-fluorophenyl)-5-(3,4,5-trimethoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (1b) and 3-(4-chlorophenyl)-5-(3,4,5-trimethoxythiphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2b) showed the best activity against HepG-2 cells, with IC50 values of 6.78 μM and 16.02 μM, respectively. They also displayed potent activity against Hela cells; meanwhile, 3-(4-chlorophenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (5b) and 3-(4-bromo-phenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b) were also identified as promising anticancer agents against A549 cells owing to their notable inhibitory effect, compared with cisplatin (IC50 = 29.48 μM). Furthermore, it was also found that compounds 1b and 2b had low cytotoxicity against NIH/3T3 cells and further mechanistic studies revealed that 1b arrested HepG-2 cells cycle at the G2/M phase at high concentrations and induced apoptosis in HepG-2 cells. Moreover, 1b upregulated protein expression level of cleaved caspase-3, cleaved PARP, Bax and p53 and downregulated protein expression level of Bcl-2 in dose-dependent way in HepG-2 cells. Thus, this study indicates that compound 1b might be a promising antitumor drug candidate. Full article
Figures

Figure 1

Open AccessArticle Fabrication of Antimicrobial Peptide-Loaded PLGA/Chitosan Composite Microspheres for Long-Acting Bacterial Resistance
Molecules 2017, 22(10), 1637; doi:10.3390/molecules22101637
Received: 14 September 2017 / Revised: 23 September 2017 / Accepted: 25 September 2017 / Published: 29 September 2017
PDF Full-text (4693 KB) | HTML Full-text | XML Full-text
Abstract
An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH2), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the
[...] Read more.
An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH2), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the release of KSL-W for long-term bacterial resistance, KSL-W-loaded PLGA/chitosan composite microspheres (KSL/PLGA/CS MSs) were prepared by electrospraying and combined crosslinking-emulsion methods. Different formulations of microspheres were characterized as to surface morphology, size distribution, encapsulation efficiency, in vitro drug release, and antimicrobial activity. Antibacterial experiment demonstrated the prolonged antimicrobial and inhibitory effects of KSL/PLGA/CS MSs on oral bacteria. Moreover, the cell proliferation assay proved that the released KSL-W antibacterial dosage had no cytotoxicity to the growth of osteoblast MC3T3-E1. Thus, our study suggested that the KSL-W-loaded PLGA/CS composite microspheres may have potentially therapeutic applications as an effective drug delivery system in the treatment of oral infectious diseases such as periodontitis and periodontitis, and also within bone graft substitutes for alveolar bone augmentation. Full article
(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)
Figures

Open AccessArticle Bioassay-Guided Isolated Compounds from Morinda officinalis Inhibit Alzheimer’s Disease Pathologies
Molecules 2017, 22(10), 1638; doi:10.3390/molecules22101638
Received: 20 September 2017 / Revised: 28 September 2017 / Accepted: 28 September 2017 / Published: 29 September 2017
PDF Full-text (963 KB) | HTML Full-text | XML Full-text
Abstract
Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease,
[...] Read more.
Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, M. officinalis has not been evaluated in an AD bioassay. Therefore, M. officinalis extracts and fractions were tested for AD-related activity, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. A bioassay-guided approach led to isolation of 10 active compounds, eight anthraquinones (18), one coumarin (9), and one phytosterol (10), from n-hexane and ethyl acetate fractions of M. officinalis. The five anthraquinones (48) were stronger inhibitors of AChE than were other compounds. Compounds 3 and 9 were good inhibitors of BChE, and compounds 3 and 8 were good inhibitors of BACE1. Compounds 15 and 79 were more active than the positive control in inhibiting AGE formation. In addition, we first suggested a structure-activity relationship by which anthraquinones inhibit AChE and BACE1. Our findings demonstrate the preventive and therapeutic efficacy of M. officinalis for AD and its potential use as a natural alternative medicine. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin
Molecules 2017, 22(10), 1639; doi:10.3390/molecules22101639
Received: 4 August 2017 / Revised: 26 September 2017 / Accepted: 26 September 2017 / Published: 29 September 2017
PDF Full-text (5665 KB) | HTML Full-text | XML Full-text
Abstract
Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying
[...] Read more.
Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying mechanisms. The in vitro results indicated that K36H reduced UVB-induced mitogen-activated protein kinase (MAP kinase) expression. Furthermore, K36H treatment reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated fibroblasts by regulating IκB and nuclear factor-kappa B (NF-κB) expression. In the animal study, topically applied K36H markedly reduced inflammation and skin thickness and prevented photodamage to the skin of hairless mice. In addition, K36H inhibited the levels of UV-upregulated inflammation-related proteins levels such as IL-1, iNOS, and NF-κB in the dermis of hairless mice. Our findings demonstrated the antioxidant and anti-inflammatory properties of K36H in human skin fibroblasts and hairless mice. Therefore, K36H can be developed as an antiphotodamage and antiphotoinflammation agent. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
Figures

Figure 1

Open AccessArticle Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines
Molecules 2017, 22(10), 1641; doi:10.3390/molecules22101641
Received: 8 September 2017 / Revised: 27 September 2017 / Accepted: 28 September 2017 / Published: 29 September 2017
PDF Full-text (1049 KB) | HTML Full-text | XML Full-text
Abstract
Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their
[...] Read more.
Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity. Full article
(This article belongs to the Special Issue Peptide Therapeutics)
Figures

Open AccessArticle Nonempirical Simulations of Inhomogeneous Broadening of Electronic Transitions in Solution: Predicting Band Shapes in One- and Two-Photon Absorption Spectra of Chalcones
Molecules 2017, 22(10), 1643; doi:10.3390/molecules22101643
Received: 17 August 2017 / Revised: 20 September 2017 / Accepted: 21 September 2017 / Published: 30 September 2017
PDF Full-text (1405 KB) | HTML Full-text | XML Full-text
Abstract
We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as
[...] Read more.
We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as rigid, flexible or partly-flexible (restrained) body. The first approach, termed RBMD-PE-TDDFT, was employed to estimate the inhomogeneous broadening for subsequent convolution with the vibrationally-resolved spectra of the molecule in solution determined quantum-mechanically (QM). As demonstrated, the RBMD-PE-TDDFT/QM-PCM approach delivers accurate band widths, also reproducing their correct asymmetric shapes. Further refinement can be obtained by the estimation of the inhomogeneous broadening using the RBMD-PERI-CC2 method. On the other hand, the remaining two approaches (FBMD-PE-TDDFT and ResBMD-PE-TDDFT), which lack quantum-mechanical treatment of molecular vibrations, lead to underestimated band widths. In this study, we also proposed a simple strategy regarding the rapid selection of the exchange-correlation functional for the simulations of vibrationally-resolved one- and two-photon absorption spectra based on two easy-to-compute metrics. Full article
Figures

Open AccessArticle Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents
Molecules 2017, 22(10), 1644; doi:10.3390/molecules22101644
Received: 15 September 2017 / Revised: 21 September 2017 / Accepted: 27 September 2017 / Published: 30 September 2017
PDF Full-text (2736 KB) | HTML Full-text | XML Full-text
Abstract
A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than
[...] Read more.
A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC99 values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents. Full article
(This article belongs to the Special Issue Versatile Coumarins)
Figures

Open AccessArticle Melandrii Herba Extract Attenuates H2O2-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells and Scopolamine-Induced Memory Impairment in Mice
Molecules 2017, 22(10), 1646; doi:10.3390/molecules22101646
Received: 29 August 2017 / Revised: 20 September 2017 / Accepted: 26 September 2017 / Published: 30 September 2017
PDF Full-text (5103 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H2O2-induced neurotoxicity via caspase-3
[...] Read more.
Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H2O2-induced neurotoxicity via caspase-3 inactivation, Bcl-2 downregulation, Bax upregulation, and MAPK activation (ERK 1/2, JNK 1/2, and p38 MAPK) in vitro. Moreover, our in vivo data showed that ME was able to attenuate scopolamine-induced cognitive impairment. These results provide in vitro and in vivo evidence that ME exhibits neuroprotective properties against oxidative stress, which suggests that ME is worthy of further investigation as a complementary, or even as an alternative, product for preventing and treating neurodegenerative disorders. Full article
(This article belongs to the Section Natural Products)
Figures

Figure 1

Open AccessArticle The Effect of Different Starch Liberation and Saccharification Methods on the Microbial Contaminations of Distillery Mashes, Fermentation Efficiency, and Spirits Quality
Molecules 2017, 22(10), 1647; doi:10.3390/molecules22101647
Received: 6 September 2017 / Revised: 27 September 2017 / Accepted: 29 September 2017 / Published: 30 September 2017
PDF Full-text (286 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate the influence of different starch liberation and saccharification methods on microbiological contamination of distillery mashes. Moreover, the effect of hop α-acid preparation for protection against microbial infections was assessed. The quality of agricultural distillates was
[...] Read more.
The aim of this study was to evaluate the influence of different starch liberation and saccharification methods on microbiological contamination of distillery mashes. Moreover, the effect of hop α-acid preparation for protection against microbial infections was assessed. The quality of agricultural distillates was also evaluated. When applying the pressureless liberation of starch (PLS) and malt as a source of amylolytic enzymes, the lactic acid bacteria count in the mashes increased several times during fermentation. The mashes obtained using the pressure-thermal method and malt enzymes revealed a similar pattern. Samples prepared using cereal malt exhibited higher concentrations of lactic and acetic acids, as compared to mashes prepared using enzymes of microbial origin. The use of hop α-acids led to the reduction of bacterial contamination in all tested mashes. As a result, fermentation of both mashes prepared with microbial origin enzyme preparations and with barley malt resulted in satisfactory efficiency and distillates with low concentrations of aldehydes. Full article
Figures

Open AccessArticle Complex Enzyme-Assisted Extraction Releases Antioxidative Phenolic Compositions from Guava Leaves
Molecules 2017, 22(10), 1648; doi:10.3390/molecules22101648
Received: 13 September 2017 / Revised: 26 September 2017 / Accepted: 26 September 2017 / Published: 30 September 2017
PDF Full-text (1456 KB) | HTML Full-text | XML Full-text
Abstract
Phenolics in food and fruit tree leaves exist in free, soluble-conjugate, and insoluble-bound forms. In this study, in order to enhance the bioavailability of insoluble-bound phenolics from guava leaves (GL), the ability of enzyme-assisted extraction in improving the release of insoluble-bound phenolics was
[...] Read more.
Phenolics in food and fruit tree leaves exist in free, soluble-conjugate, and insoluble-bound forms. In this study, in order to enhance the bioavailability of insoluble-bound phenolics from guava leaves (GL), the ability of enzyme-assisted extraction in improving the release of insoluble-bound phenolics was investigated. Compared to untreated GL, single xylanase-assisted extraction did not change the composition and yield of soluble phenolics, whereas single cellulase or β-glucosidase-assisted extraction significantly enhanced the soluble phenolics content of PGL. However, complex enzyme-assisted extraction (CEAE) greatly improved the soluble phenolics content, flavonoids content, ABTS, DPPH, and FRAP by 103.2%, 81.6%, 104.4%, 126.5%, and 90.3%, respectively. Interestingly, after CEAE, a major proportion of phenolics existed in the soluble form, and rarely in the insoluble-bound form. Especially, the contents of quercetin and kaempferol with higher bio-activity were enhanced by 3.5- and 2.2-fold, respectively. More importantly, total soluble phenolics extracts of GL following CEAE exhibited the highest antioxidant activity and protective effect against supercoiled DNA damage. This enzyme-assisted extraction technology can be useful for extracting biochemical components from plant matrix, and has good potential for use in the food and pharmaceutical industries. Full article
Figures

Open AccessArticle Inhibitory Effects of Total Triterpenoid Saponins Isolated from the Seeds of the Tea Plant (Camellia sinensis) on Human Ovarian Cancer Cells
Molecules 2017, 22(10), 1649; doi:10.3390/molecules22101649
Received: 23 August 2017 / Revised: 17 September 2017 / Accepted: 28 September 2017 / Published: 30 September 2017
PDF Full-text (5304 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer is regarded as one of the most severe malignancies for women in the world. Death rates have remained steady over the past five decades, due to the undeniable inefficiency of the current treatment in preventing its recurrence and death. The development
[...] Read more.
Ovarian cancer is regarded as one of the most severe malignancies for women in the world. Death rates have remained steady over the past five decades, due to the undeniable inefficiency of the current treatment in preventing its recurrence and death. The development of new effective alternative agents for ovarian cancer treatment is becoming increasingly critical. Tea saponins (TS) are triterpenoidsaponins composed of sapogenins, glycosides, and organic acids, which possess a variety of pharmacological activities, and have shown promise in the anti-cancer field. Through cell CellTiter 96® Aqueous One Solution Cell Proliferation assay (MTS) assay, colony formation, Hoechst 33342 staining assay, caspase-3/7 activities, flow cytometry for apoptosis analysis, and Western blot, we observed that TS isolated from the seeds of tea plants, Camellia sinensis, exhibited strong anti-proliferation inhibitory effects on OVCAR-3 and A2780/CP70 ovarian cancer cell lines. Our results indicate that TS may selectivity inhibit human ovarian cancer cells by mediating apoptosis through the extrinsic pathway, and initiating anti-angiogenesis via decreased VEGF protein levels in a HIF-1α-dependent pathway. Our data suggests that, in the future, TS could be incorporated into a potential therapeutic agent against human ovarian cancer. Full article
Figures

Figure 1

Open AccessArticle Synthesis of Disaccharide Nucleosides Utilizing the Temporary Protection of the 2′,3′-cis-Diol of Ribonucleosides by a Boronic Ester
Molecules 2017, 22(10), 1650; doi:10.3390/molecules22101650
Received: 8 September 2017 / Revised: 24 September 2017 / Accepted: 29 September 2017 / Published: 1 October 2017
PDF Full-text (2227 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Disaccharide nucleosides are an important class of natural compounds that have a variety of biological activities. In this study, we report on the synthesis of disaccharide nucleosides utilizing the temporary protection of the 2′,3′-cis-diol of ribonucleosides, such as adenosine, guanosine, uridine,
[...] Read more.
Disaccharide nucleosides are an important class of natural compounds that have a variety of biological activities. In this study, we report on the synthesis of disaccharide nucleosides utilizing the temporary protection of the 2′,3′-cis-diol of ribonucleosides, such as adenosine, guanosine, uridine, 5-metyluridine, 5-fluorouridine and cytidine, by a boronic ester. The temporary protection of the above ribonucleosides permits the regioselective O-glycosylation of the 5’-hydroxyl group with thioglycosides using a p-toluenesulfenyl chloride (p-TolSCl)/silver triflate (AgOTf) promoter system to afford the corresponding disaccharide nucleosides in fairly good chemical yields. The formation of a boronic ester prepared from uridine and 4-(trifluoromethyl)phenylboronic acid was examined by 1H, 11B and 19F NMR spectroscopy. Full article
(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)
Figures

Figure 1

Open AccessArticle 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
Molecules 2017, 22(10), 1651; doi:10.3390/molecules22101651
Received: 16 August 2017 / Revised: 20 September 2017 / Accepted: 29 September 2017 / Published: 1 October 2017
PDF Full-text (2141 KB) | HTML Full-text | XML Full-text
Abstract
The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission
[...] Read more.
The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of Aβ oligomer from Aβ peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and Aβ peptide, which might prevent the conformational transition and oligomerization of Aβ peptide. Moreover, Aβ oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal Aβ oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD. Full article
(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)
Figures

Figure 1

Open AccessArticle Characterization of the Ornithine Hydroxylation Step in Albachelin Biosynthesis
Molecules 2017, 22(10), 1652; doi:10.3390/molecules22101652
Received: 7 September 2017 / Revised: 27 September 2017 / Accepted: 28 September 2017 / Published: 1 October 2017
PDF Full-text (1739 KB) | HTML Full-text | XML Full-text
Abstract
N-Hydroxylating monooxygenases (NMOs) are involved in siderophore biosynthesis. Siderophores are high affinity iron chelators composed of catechol and hydroxamate functional groups that are synthesized and secreted by microorganisms and plants. Recently, a new siderophore named albachelin was isolated from a culture of
[...] Read more.
N-Hydroxylating monooxygenases (NMOs) are involved in siderophore biosynthesis. Siderophores are high affinity iron chelators composed of catechol and hydroxamate functional groups that are synthesized and secreted by microorganisms and plants. Recently, a new siderophore named albachelin was isolated from a culture of Amycolatopsis alba growing under iron-limiting conditions. This work focuses on the expression, purification, and characterization of the NMO, abachelin monooxygenase (AMO) from A. alba. This enzyme was purified and characterized in its holo (FAD-bound) and apo (FAD-free) forms. The apo-AMO could be reconstituted by addition of free FAD. The two forms of AMO hydroxylate ornithine, while lysine increases oxidase activity but is not hydroxylated and display low affinity for NADPH. Full article
(This article belongs to the Special Issue Flavoenzymes)
Figures

Figure 1

Open AccessArticle A Comparative Genomic and Transcriptomic Survey Provides Novel Insights into N-Acetylserotonin Methyltransferase (ASMT) in Fish
Molecules 2017, 22(10), 1653; doi:10.3390/molecules22101653
Received: 14 September 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 2 October 2017
PDF Full-text (5217 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic
[...] Read more.
Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic survey to explore the ASMT family in fish. Two ASMT isotypes (ASMT1 and ASMT2) and a new ASMT-like (ASMTL) are all extracted from teleost genomes on the basis of phylogenetic and synteny analyses. We confirmed that C-terminal of the ASMTL proteins (ASMTL-ASMT) is homology to the full length of ASMT1 and ASMT2. Our results also demonstrate that the two ASMT isotypes and their distribution in teleosts seem to be the result of combinations of whole-genome duplication (WGD) and gene loss. Differences were also observed in tissue distribution and relative transcript abundances of ASMT1, ASMT2 and ASMTL through transcriptomic analysis. Protein sequence alignment and 3D structure prediction of ASMTs and ASMTL suggest differential roles for these ASMT genes. In summary, our current work provides novel insights into the ASMT genes in fish by combination of genomic and transcriptomic data. Full article
Figures

Open AccessArticle Protective Effects of Parkia biglobosa Protein Isolate on Streptozotocin-Induced Hepatic Damage and Oxidative Stress in Diabetic Male Rats
Molecules 2017, 22(10), 1654; doi:10.3390/molecules22101654
Received: 27 August 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 2 October 2017
PDF Full-text (2269 KB) | HTML Full-text | XML Full-text
Abstract
This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats
[...] Read more.
This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Diabetic rats were orally treated daily with PBPi (200 or 400 mg/kg body weight) or insulin (5 U/kg, i.p.) for 28 days. The degree of protection was evaluated using biochemical parameters such as malondialdehyde (MDA) levels, serum transaminases (ALT and AST), total protein, total glutathione (Total GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and interleukin-6 (IL-6) activities. Histology of liver sections was also performed. The HPLC fingerprint of PBPi revealed eleven distinct peaks; PBPi at tested doses significantly attenuates STZ-induced elevated levels of serum IL-6, ALT and AST; and hepatic TBARS levels. Hepatic antioxidants (Total GSH, GST, SOD, CAT) as well as total protein were markedly restored in a dose-dependent manner. Histopathological results strongly support the protective role of PBPi. These results suggest PBPi could confer protection by ameliorating hepatic damage and oxidative stress caused by STZ in animal model possibly via its anti-inflammatory and antioxidant properties. Full article
Figures

Open AccessArticle Influence of Plant Growth Retardants on Quality of Codonopsis Radix
Molecules 2017, 22(10), 1655; doi:10.3390/molecules22101655
Received: 8 September 2017 / Revised: 28 September 2017 / Accepted: 1 October 2017 / Published: 9 October 2017
PDF Full-text (1081 KB) | HTML Full-text | XML Full-text
Abstract
Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous
[...] Read more.
Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous Chinese traditional herb. However, it is still unclear whether PGR affects the medicinal quality of C. Radix. In the present study, amino acid analyses, targeted and non-targeted analyses by ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS) and gas chromatography-MS were used to analyze and compare the composition of untreated C. Radix and C. Radix treated with PGR. The contents of two key bioactive compounds, lobetyolin and atractylenolide III, were not affected by PGR treatment. The amounts of polysaccharides and some internal volatiles were significantly decreased by PGR treatment; while the free amino acids content was generally increased. Fifteen metabolites whose abundance were affected by PGR treatment were identified by UPLC-TOF-MS. Five of the up-regulated compounds have been reported to show immune activity, which might contribute to the healing efficacy (“buqi”) of C. Radix. The results of this study showed that treatment of C. Radix with PGR during cultivation has economic benefits and affected some main bioactive compounds in C. Radix. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Figure 1

Open AccessArticle Comparison of the Effectiveness of Water-Based Extraction of Substances from Dry Tea Leaves with the Use of Magnetic Field Assisted Extraction Techniques
Molecules 2017, 22(10), 1656; doi:10.3390/molecules22101656
Received: 19 September 2017 / Revised: 29 September 2017 / Accepted: 29 September 2017 / Published: 3 October 2017
PDF Full-text (870 KB) | HTML Full-text | XML Full-text
Abstract
This article presents the findings of a study investigating the feasibility of using a magnetic field assisted technique for the water-based extraction of mineral components, polyphenols, and caffeine from dry black and green tea leaves. The authors present a concept of applying constant
[...] Read more.
This article presents the findings of a study investigating the feasibility of using a magnetic field assisted technique for the water-based extraction of mineral components, polyphenols, and caffeine from dry black and green tea leaves. The authors present a concept of applying constant and variable magnetic fields in the process of producing water-based infusions from selected types of tea. Analyses investigating the effectiveness of the proposed technique in comparison with conventional infusion methods assessed the contents of selected mineral components—i.e., Al, Ca, Cu, K, Mg, P, S, and Zn—which were examined with the use of ICP-OES. The contents of caffeine and polyphenolic compounds were assessed using the HPLC. A changing magnetic field permitted an increased effectiveness of extraction of the mineral components, caffeine, and polyphenols. The findings support the conclusion that a changing magnetic field assisted extraction method is useful for obtaining biologically valuable components from tea infusions. Full article
Figures

Figure 1

Open AccessArticle Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR Signaling Pathway
Molecules 2017, 22(10), 1657; doi:10.3390/molecules22101657
Received: 30 August 2017 / Revised: 29 September 2017 / Accepted: 29 September 2017 / Published: 3 October 2017
PDF Full-text (4420 KB) | HTML Full-text | XML Full-text
Abstract
Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as
[...] Read more.
Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6), a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood. The aim of the in vitro study was to investigate the anticancer activity of InsP6 on colon cancer with the focus on inhibiting the AKT1 kinase and p70S6K1 as mTOR effector, in relation to proliferation and apoptosis of cells. The colon cancer Caco-2 cells were cultured using standard techniques and exposed to InsP6 at different concentrations (1 mM, 2.5 mM and 5 mM). Cellular proliferative activity was monitored by 5-bromo-2′-deoxyuridine (BrdU) incorporation into cellular DNA. Flow cytometric analysis was performed for cell cycle progression and apoptosis studies. Real-time RT-qPCR was used to validate mRNA levels of CDNK1A, CDNK1B, CASP3, CASP9, AKT1 and S6K1 genes. The concentration of p21 protein as well as the activities of caspase 3, AKT1 and p70S6K1 were determined by the ELISA method. The results revealed that IP6 inhibited proliferation and stimulated apoptosis of colon cancer cells. This effect was mediated by an increase in the expression of genes encoding p21, p27, caspase 3, caspase 9 as well a decrease in transcription of AKT1 and S6K1. InsP6 suppressed phosphorylation of AKT1 and p70S6K1, downstream effector of mTOR. Based on these studies it may be concluded that InsP6 can reduce proliferation and induce apoptosis through inhibition of the AKT/mTOR pathway and mTOR effector followed by modulation of the expression and activity of several key components of these pathways in colon cancer cells. Full article
Figures

Figure 1

Open AccessArticle Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
Molecules 2017, 22(10), 1658; doi:10.3390/molecules22101658
Received: 20 August 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 3 October 2017
PDF Full-text (14022 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene
[...] Read more.
N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC50 = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Effect of High-Pressure Treatment on Catalytic and Physicochemical Properties of Pepsin
Molecules 2017, 22(10), 1659; doi:10.3390/molecules22101659
Received: 19 September 2017 / Revised: 29 September 2017 / Accepted: 2 October 2017 / Published: 11 October 2017
PDF Full-text (2075 KB) | HTML Full-text | XML Full-text
Abstract
For a long time, high-pressure treatment has been used to destroy the compact structures of natural proteins in order to promote subsequent enzymatic hydrolysis. However, there are few reports evaluating the feasibility of directly improving the catalytic capability of proteases by using high-pressure
[...] Read more.
For a long time, high-pressure treatment has been used to destroy the compact structures of natural proteins in order to promote subsequent enzymatic hydrolysis. However, there are few reports evaluating the feasibility of directly improving the catalytic capability of proteases by using high-pressure treatments. In this study, the effects of high-pressure treatment on the catalytic capacity and structure of pepsin were investigated, and the relationship between its catalytic properties and changes in its physicochemical properties was explored. It was found that high-pressure treatment could lead to changes of the sulfhydryl group/disulfide bond content, hydrophobicity, hydrodynamic radius, intrinsic viscosity, and subunit composition of pepsin, and the conformational change of pepsin resulted in improvement to its enzymatic activity and hydrolysis efficiency, which had an obvious relationship with the high-pressure treatment conditions. Full article
Figures

Figure 1

Open AccessArticle Selective O-Alkylation of the Crown Conformer of Tetra(4-hydroxyphenyl)calix[4]resorcinarene to the Corresponding Tetraalkyl Ether
Molecules 2017, 22(10), 1660; doi:10.3390/molecules22101660
Received: 10 September 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 4 October 2017
PDF Full-text (1524 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were
[...] Read more.
Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were carried out with pure conformers, and it was observed that the reaction between tetra(4-hydroxyphenyl)calix[4]resorcinarene fixed in the chair conformation does not occur, while for the molecule fixed in the crown conformation only one tetraalkylated derivative was obtained. The obtained product was characterized using IR, 1H-NMR, 13C-NMR, COSY, HMQC and HMBC techniques. An exhaustive NMR study showed that the reaction is selective at the hydroxyl groups in the lower rim, without affecting the hydroxyl groups in the upper rim. In addition, the RP–HPLC analysis of the epoxidation reaction mixture, using both crown and chair conformers, showed that only the crown conformer reacted under tested conditions. Finally, a comparative study of the reactivity of tetranonylcalix[4]resorcinarene with glycidyl methacrylate showed that the reaction does not take place. Instead, the formation of the tetranonylcalix[4]resorcinarene tetrasodium salt was observed, which confirms that the hydroxyl groups in the upper rim are unreactive under these conditions. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Figure 1

Open AccessArticle In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates
Molecules 2017, 22(10), 1661; doi:10.3390/molecules22101661
Received: 26 September 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 4 October 2017
PDF Full-text (3202 KB) | HTML Full-text | XML Full-text
Abstract
The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio
[...] Read more.
The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
Figures

Figure 1

Open AccessArticle Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007–2012 Korea National Health and Nutrition Examination Survey
Molecules 2017, 22(10), 1664; doi:10.3390/molecules22101664
Received: 31 August 2017 / Revised: 29 September 2017 / Accepted: 2 October 2017 / Published: 5 October 2017
PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national
[...] Read more.
Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national representative data. A total of 24,377 adults (19–74 years) who completed one-day 24 h dietary recall and health examination were included. Dietary antioxidant intakes including α-carotene (p < 0.0001), lycopene (p = 0.0107), flavan-3-ols (p < 0.0001), and proanthocyanidins (p = 0.0075) were significantly higher in non-diabetic subjects than in diabetic subjects. After adjusting for confounding variables, the highest quartile group of α-carotene intake was associated with a 48% reduced risk of T2D in men (OR: 0.52, 95% CI: 0.34–0.80, p for trend = 0.0037) and a 39% reduced risk in women (OR: 0.61, 95% CI: 0.38–0.996, p for trend = 0.0377) compared to the lowest quartile group. Men in the highest quartile of β-carotene intake showed lower risk of T2D (OR: 0.64, 95% CI: 0.42–0.97), but no significant decreasing trend. However, the intakes of total carotenoids and other antioxidants showed no significant association with the risk of T2D. These findings suggest that a further comprehensive approach which considers overall dietary pattern is required. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
Open AccessArticle Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities
Molecules 2017, 22(10), 1666; doi:10.3390/molecules22101666
Received: 1 September 2017 / Revised: 29 September 2017 / Accepted: 3 October 2017 / Published: 7 October 2017
PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal
[...] Read more.
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle A Theoretical Study of the N to O Linkage Photoisomerization Efficiency in a Series of Ruthenium Mononitrosyl Complexes
Molecules 2017, 22(10), 1667; doi:10.3390/molecules22101667
Received: 8 September 2017 / Revised: 29 September 2017 / Accepted: 3 October 2017 / Published: 6 October 2017
PDF Full-text (2272 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans-[RuCl(NO)(py)4]2+, trans-[RuBr(NO)(py)4]2+, and trans-(Cl,Cl)[RuCl2(NO)(tpy)]
[...] Read more.
Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans-[RuCl(NO)(py)4]2+, trans-[RuBr(NO)(py)4]2+, and trans-(Cl,Cl)[RuCl2(NO)(tpy)]+, has been investigated using density functional theory and time-dependent density functional theory. The N to O photoisomerization pathways and absorption properties of the various stable and metastable species have been computed, providing a simple rationalization of the photoconversion trend in this series of complexes. The dramatic decrease of the N to O photoisomerization efficiency going from the first to the last complex is mainly attributed to an increase of the photoproduct absorption at the irradiation wavelength, rather than a change in the photoisomerization pathways. Full article
Figures

Figure 1

Open AccessArticle Two-Dimensional Capillary Electrophoresis with On-Line Sample Preparation and Cyclodextrin Separation Environment for Direct Determination of Serotonin in Human Urine
Molecules 2017, 22(10), 1668; doi:10.3390/molecules22101668
Received: 26 September 2017 / Revised: 3 October 2017 / Accepted: 4 October 2017 / Published: 7 October 2017
PDF Full-text (1407 KB) | HTML Full-text | XML Full-text
Abstract
An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm)
[...] Read more.
An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm) were chosen for the possibility to enhance the sample load capacity, and, by that, to decrease limit of detection. Isotachophoresis served for the sample preseparation, defined elimination of sample matrix constituents (sample clean up), and preconcentration of the analyte. Cyclodextrin separation environment enhanced separation selectivity of capillary zone electrophoresis. In this way, serotonin could be successfully separated from the rest of the sample matrix constituents migrating in capillary zone electrophoresis step so that human urine could be directly (i.e., without any external sample preparation) injected into the analyzer. The proposed method was successfully validated, showing favorable parameters of sensitivity (limit of detection for serotonin was 2.32 ng·mL−1), linearity (regression coefficient higher than 0.99), precision (repeatability of the migration time and peak area were in the range of 0.02–1.17% and 5.25–7.88%, respectively), and recovery (ranging in the interval of 90.0–93.6%). The developed method was applied for the assay of the human urine samples obtained from healthy volunteers. The determined concentrations of serotonin in such samples were in the range of 12.4–491.2 ng·mL−1 that was in good agreement with literature data. This advanced method represents a highly effective, reliable, and low-cost alternative for the routine determination of serotonin as a biomarker in human urine. Full article
Figures

Figure 1

Open AccessArticle Rosmarinic Acid, a Rosemary Extract Polyphenol, Increases Skeletal Muscle Cell Glucose Uptake and Activates AMPK
Molecules 2017, 22(10), 1669; doi:10.3390/molecules22101669
Received: 9 August 2017 / Revised: 30 September 2017 / Accepted: 3 October 2017 / Published: 7 October 2017
PDF Full-text (3806 KB) | XML Full-text
Abstract
Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in
[...] Read more.
Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 µM) increased glucose uptake (186 ± 4.17% of control, p < 0.001) to levels comparable to maximum insulin (204 ± 10.73% of control, p < 0.001) and metformin (202 ± 14.37% of control, p < 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RA-stimulated glucose uptake was inhibited by the AMPK inhibitor compound C and was not affected by wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). The current study shows an effect of RA to increase muscle glucose uptake and AMPK phosphorylation. RA deserves further study as it shows potential to be used as an agent to regulate glucose homeostasis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents
Molecules 2017, 22(10), 1670; doi:10.3390/molecules22101670
Received: 24 August 2017 / Revised: 28 September 2017 / Accepted: 28 September 2017 / Published: 8 October 2017
PDF Full-text (6778 KB) | HTML Full-text | XML Full-text
Abstract
Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain
[...] Read more.
Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy-methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Open AccessArticle Predictive QSAR Models for the Toxicity of Disinfection Byproducts
Molecules 2017, 22(10), 1671; doi:10.3390/molecules22101671
Received: 26 September 2017 / Revised: 30 September 2017 / Accepted: 1 October 2017 / Published: 9 October 2017
PDF Full-text (875 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of
[...] Read more.
Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of an in-silico model of toxicology endpoints of DBPs is rarely studied. The main aim of the present study is to develop predictive quantitative structure–activity relationship (QSAR) models for the reactive toxicities of 50 DBPs in the five bioassays of X-Microtox, GSH+, GSH−, DNA+ and DNA−. All-subset regression was used to select the optimal descriptors, and multiple linear-regression models were built. The developed QSAR models for five endpoints satisfied the internal and external validation criteria: coefficient of determination (R2) > 0.7, explained variance in leave-one-out prediction (Q2LOO) and in leave-many-out prediction (Q2LMO) > 0.6, variance explained in external prediction (Q2F1, Q2F2, and Q2F3) > 0.7, and concordance correlation coefficient (CCC) > 0.85. The application domains and the meaning of the selective descriptors for the QSAR models were discussed. The obtained QSAR models can be used in predicting the toxicities of the 50 DBPs. Full article
(This article belongs to the Section Molecular Diversity)
Figures

Figure 1

Open AccessArticle Design, Synthesis and Antifungal Activity of Psoralen Derivatives
Molecules 2017, 22(10), 1672; doi:10.3390/molecules22101672
Received: 3 September 2017 / Accepted: 4 October 2017 / Published: 9 October 2017
PDF Full-text (1341 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by 1H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal
[...] Read more.
A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by 1H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Botrytis cinerea, Alternaria solani, Gibberella zeae, Cucumber anthrax, and Alternaria leaf spot at 100 μg/mL, and some of the designed compounds exhibited potential antifungal activities. Compound 3a (67.9%) exhibited higher activity than the control Osthole (66.1%) against Botrytis cinerea. Furthermore, compound 4b (62.4%) represented equivalent antifungal activity as Osthole (69.5%) against Rhizoctonia solani. The structure-activity relationship (SAR) study demonstrates that linear furanocoumarin moiety has an important effect on the antifungal activity, promoting the idea of the coumarin ring as a framework that might be exploited in the future. Full article
Figures

Open AccessArticle Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure
Molecules 2017, 22(10), 1673; doi:10.3390/molecules22101673
Received: 14 August 2017 / Revised: 24 September 2017 / Accepted: 24 September 2017 / Published: 9 October 2017
PDF Full-text (824 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis
[...] Read more.
Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein structure features. To address this problem, here we introduce an index to quantify the protein-function criticality of a residue based on experimental data and a strategy aimed to optimize both, descriptors of protein structure (physicochemical and centrality descriptors) and machine learning algorithms, to minimize the error in the classification of critical residues. We observed that both physicochemical and centrality descriptors of residues effectively relate protein structure and protein function, and that physicochemical descriptors better describe critical residues. We also show that critical residues are better classified when residue criticality is considered as a binary attribute (i.e., residues are considered critical or not critical). Using this binary annotation for critical residues 8 models rendered accurate and non-overlapping classification of critical residues, confirming the multi-factorial character of the structure-function relationship of proteins. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Figure 1

Open AccessArticle Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum
Molecules 2017, 22(10), 1674; doi:10.3390/molecules22101674
Received: 18 September 2017 / Revised: 5 October 2017 / Accepted: 6 October 2017 / Published: 9 October 2017
PDF Full-text (1240 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies
[...] Read more.
Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies on the secondary metabolite production of this strain in various culture media revealed that the major components from shake flasks were massarilactones D (1) and H (2) as well as two new furanone derivatives for which we propose the trivial names (5S)-cis-gregatin B (3) and graminin D (4). Scale-up of the fermentation in a 10 L bioreactor yielded massarilactone D and several further metabolites. Among those were three new anthranilic acid derivatives (57), two known anthranilic acid analogues (8 and 9) and three cyclopeptides (1012). Their structures were elucidated on the basis of extensive spectroscopic analysis (1D- and 2D-NMR), high-resolution mass spectrometry (HRESIMS), and the application of the modified Mosher’s method. The isolated metabolites were tested for antimicrobial and cytotoxic activities against various bacteria, fungi, and two mammalian cell lines. The new Metabolite 5 and Compound 9 exhibited antimicrobial activity while Compound 9 showed cytotoxicity activity against KB3.1 cells. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Gypmacrophin A, a Rare Pentacyclic Sesterterpenoid, Together with Three Depsides, Functioned as New Chemical Evidence for Gypsoplaca macrophylla (Zahlbr.) Timdal Identification
Molecules 2017, 22(10), 1675; doi:10.3390/molecules22101675
Received: 18 September 2017 / Revised: 30 September 2017 / Accepted: 3 October 2017 / Published: 9 October 2017
PDF Full-text (1228 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The phytochemical investigation on 1 g of materials from Gypsoplaca macrophylla (Zahlbr.) Timdal resulted in the discovery of gypmacrophin A, a rare pentacyclic sesterterpenoid; brialmontin III, a new polysubstituted depside and two known ones, brialmontins I and II. The structure and absolute configurations
[...] Read more.
The phytochemical investigation on 1 g of materials from Gypsoplaca macrophylla (Zahlbr.) Timdal resulted in the discovery of gypmacrophin A, a rare pentacyclic sesterterpenoid; brialmontin III, a new polysubstituted depside and two known ones, brialmontins I and II. The structure and absolute configurations of gypmacrophin A were elucidated by spectroscopic analyses and computational methods. Gypmacrophin A showed weak inhibition of AchE with an IC50 value of 32.03 μM. The four compounds provided new chemical evidence for G. macrophylla identification. Full article
(This article belongs to the Special Issue Diversity of Terpenoids)
Figures

Open AccessFeature PaperArticle Exploring the Degradation of Ibuprofen by Bacillus thuringiensis B1(2015b): The New Pathway and Factors Affecting Degradation
Molecules 2017, 22(10), 1676; doi:10.3390/molecules22101676
Received: 4 September 2017 / Accepted: 6 October 2017 / Published: 9 October 2017
PDF Full-text (2728 KB) | HTML Full-text | XML Full-text
Abstract
Ibuprofen is one of the most often detected pollutants in the environment, particularly at landfill sites and in wastewaters. Contamination with pharmaceuticals is often accompanied by the presence of other compounds which may influence their degradation. This work describes the new degradation pathway
[...] Read more.
Ibuprofen is one of the most often detected pollutants in the environment, particularly at landfill sites and in wastewaters. Contamination with pharmaceuticals is often accompanied by the presence of other compounds which may influence their degradation. This work describes the new degradation pathway of ibuprofen by Bacillus thuringiensis B1(2015b), focusing on enzymes engaged in this process. It is known that the key intermediate which transformation limits the velocity of the degradation process is hydroxyibuprofen. As the degradation rate also depends on various factors, the influence of selected heavy metals and aromatic compounds on ibuprofen degradation by the B1(2015b) strain was examined. Based on the values of non-observed effect concentration (NOEC) it was found that the toxicity of tested metals increases from Hg(II) < Cu(II) < Cd(II) < Co(II) < Cr(VI). Despite the toxic effect of metals, the biodegradation of ibuprofen was observed. The addition of Co2+ ions into the medium significantly extended the time necessary for the complete removal of ibuprofen. It was shown that Bacillus thuringiensis B1(2015b) was able to degrade ibuprofen in the presence of phenol, benzoate, and 2-chlorophenol. Moreover, along with the removal of ibuprofen, degradation of phenol and benzoate was observed. Introduction of 4-chlorophenol into the culture completely inhibits degradation of ibuprofen. Full article
Figures

Open AccessArticle Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters
Molecules 2017, 22(10), 1678; doi:10.3390/molecules22101678
Received: 13 September 2017 / Accepted: 7 October 2017 / Published: 12 October 2017
PDF Full-text (669 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the
[...] Read more.
Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (E)-4n (R = β-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and Cercospora arachidicola at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7−5.5-fold more growth inhibition than its stereoisomer (Z)-4n (R = β-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (Brassica campestris) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (E)-4n (R = β-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (Z)-4n (R = β-pyridyl) which inhibited growth by 54.0%. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessFeature PaperArticle Tetraphenylpyrimidine-Based AIEgens: Facile Preparation, Theoretical Investigation and Practical Application
Molecules 2017, 22(10), 1679; doi:10.3390/molecules22101679
Received: 20 August 2017 / Accepted: 3 October 2017 / Published: 10 October 2017
PDF Full-text (5038 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to
[...] Read more.
Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to the AIE mechanism of restriction of intramolecular motion, and facilely prepared under mild reaction conditions. The photophysical property of the generated TPPM, TPPM-4M and TPPM-4P are systematically investigated and the results show that they feature the aggregation-enhanced emission (AEE) characteristics. Theoretical study shows the high-frequency bending vibrations in the central pyrimidine ring of TPPM derivatives dominate the nonradiative decay channels. Thanks to the AEE feature, their aggregates can be used to detect explosives with super-amplification quenching effects, and the sensing ability is higher than typical AIE-active tetraphenylethene. It is anticipated that TPPM derivatives could serve as a new type of widely used AIEgen based on their facile preparation and good thermo-, photo- and chemostabilities. Full article
Figures

Open AccessArticle Middle Ear Prosthesis with Bactericidal Efficacy—In Vitro Investigation
Molecules 2017, 22(10), 1681; doi:10.3390/molecules22101681
Received: 19 September 2017 / Revised: 5 October 2017 / Accepted: 6 October 2017 / Published: 10 October 2017
PDF Full-text (5853 KB) | HTML Full-text | XML Full-text
Abstract
Materials used in ossicular replacement prostheses must possess appropriate biological properties, such as biocompatibility, stability, no cytotoxicity. Due to the risk of infection (otitis media and chronic otitis media), it is desirable to use an antibacterial agent for illness prevention during the ossicular
[...] Read more.
Materials used in ossicular replacement prostheses must possess appropriate biological properties, such as biocompatibility, stability, no cytotoxicity. Due to the risk of infection (otitis media and chronic otitis media), it is desirable to use an antibacterial agent for illness prevention during the ossicular reconstruction. The goal of this work was to observe biological properties of a new composite prosthesis made of ABS containing silver nanoparticles (AgNPs 45T). Samples for biological tests and then a prototype of middle ear prosthesis were prepared using injection moulding and extrusion techniques. In vitro experiments were carried out to assess bactericidal efficacy against Staphylococcus aureus and Pseudomona aeruginosa standard strains, cell proliferation, viability and cytotoxicity, using Hs680.Tr. fibroblast cells. Surface parameters of the samples were evaluated, including roughness and wettability. The silver ions were continually released from the polymer in aqueous solution. The silver ions release was measured as increasing with time and concentration of the silver nanoparticles in the polymer matrix. No cytotoxicity effect was observed, while bactericidal efficacy was noticed for silver nanoparticles. The roughness studies showed an increase in roughness for the samples with silver nanoparticles. All polymer and composite materials containing silver nanoparticles showed hydrophilic properties. The composites were found to release silver ions at a concentration level capable of rendering the antimicrobial efficacy even with the lowest concentration of silver nanoparticles in the material. Our results demonstrate that middle ear prosthesis made of polymer and silver nanoparticles may eliminate bacteria during inflammation in the middle ear. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
Figures

Figure 1

Open AccessCommunication Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents
Molecules 2017, 22(10), 1682; doi:10.3390/molecules22101682
Received: 16 September 2017 / Revised: 27 September 2017 / Accepted: 3 October 2017 / Published: 10 October 2017
PDF Full-text (2300 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57–76% yields using CuAAC. The azido group was introduced on the
[...] Read more.
Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57–76% yields using CuAAC. The azido group was introduced on the 5′-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents. Full article
(This article belongs to the Section Bioorganic Chemistry)