Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 7 Articles
The antitumor activities of ethyl acetate extracts from Selaginella doederleinii Hieron (SD extracts) in vitro and in vivo and its\npossible mechanism were investigated. HPLC method was developed for chemical analysis. SD extracts were submitted to 3-(4,5-\ndimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on different cells, flow cytometry, and RT-PCR analysis using\nHepG2 cell and antitumor activity in vivo using H-22 xenograft tumor mice. Six biflavonoids from SD extracts were submitted to\nmolecular docking assay. The results showed that SD extracts had considerable antitumor activity in vitro and in vivo without\nobvious toxicity on normal cells and could induce cell apoptosis.The mechanisms of tumorigenesis and cell apoptosis induced by\nSD extracts may be associated with decreasing the ratio of bcl-2 and bax mRNA level, activating caspase-3, suppressing survivin,\nand decreasing the gene expression of COX-2, 5-LOX, FLAP, and 12-LOX mRNA. The main active component in SD extracts is\nbiflavonoids and some exhibited strong interactions with COX-2, 5-LOX, 12-LOX, and 15-LOX.These results offering evidence of\npossible mechanisms of SD extracts suppress cell proliferation and promote apoptosis and provide the molecular theoretical basis\nof clinical application of S. doederleinii for cancer therapy....
Aldose reductase (ALR2), a vital enzyme involved in polyol pathway, has befitted as a novel drug target in antidiabetes drug\ndiscovery process. In the present study, the binding mode and pharmacokinetic properties of potential polyphenolic compounds\nwith reported aldose reductase inhibitory activity from the genus Scrophularia have been investigated. The human ALR2 enzyme\n(PDB ID: 2FZD) acted as the receptor in the current study. Among the compounds investigated, acacetin, a methoxy flavonoid,\ndisplayed the stable binding to the active site of ALR2 with least binding energy value.Molecular interaction analysis revealed that\nacacetin interrupts the proton donation mechanism, necessary for the catalytic activity of ALR2, by forming H-bond with Tyr48\n(proton donor). In addition, acacetin also possessed favorable ADME properties and complies with Lipinski�s rule of 5 representing\nthe possible drug-like nature compared to other polyphenols. Interestingly, the biological activity predictions also ranked acacetin\nwith higher probability score for aldose reductase inhibition activity. Moreover, the molecular dynamics simulation of ALR2-\nacacetin complex was validated for the stability of ligand binding and the refined complex was used for generation of receptorligand\npharmacophore model. Thus, the molecular insights of receptor-ligand interactions gained from the present study can be\nutilized for the development of novel aldose reductase inhibitors from Scrophularia....
Citreoviridin (CIT), amycotoxin produced by Penicillium citreonigrum, is a common contaminant of wide range of agriproducts and\ndetrimental to human and animal health. In this study, the interaction of CIT with human serum albumin (HSA) is researched by\nsteady-state fluorescence, ultraviolet-visible (UV-Vis) absorption, circular dichroism (CD) methods, and molecular modeling. The\nassociation constants, binding site numbers, and corresponding thermodynamic parameters are used to investigate the quenching\nmechanism. The alternations of HSA secondary structure in the presence of CIT are demonstrated with UV-Vis, synchronous\nfluorescence, and CD spectra. The molecular modeling results reveal that CIT can bind with hydrophobic pocket of HSA with\nhydrophobic and hydrogen bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is obtained via\nfluorescence resonance energy transfer method....
Inosine 5'-monophosphate dehydrogenase (IMPDH) is one of the crucial enzymes in the de novo biosynthesis of guanosine\nnucleotides. It has served as an attractive target in immunosuppressive, anticancer, antiviral, and antiparasitic therapeutic strategies.\nIn this study, pharmacophoremapping andmolecular docking approaches were employed to discover novelHomo sapiens IMPDH\n(hIMPDH) inhibitors. The G�¨uner-Henry (GH) scoring method was used to evaluate the quality of generated pharmacophore\nhypotheses. One of the generated pharmacophore hypotheses was found to possess a GH score of 0.67. Ten potential compounds\nwere selected from the ZINC database using a pharmacophore mapping approach and docked into the IMPDH active site.We find\ntwo hits (i.e., ZINC02090792 and ZINC00048033) that match well the optimal pharmacophore features used in this investigation,\nand it is found that they forminteractions with key residues of IMPDH.We propose that these two hits are lead compounds for the\ndevelopment of novel hIMPDH inhibitors...
As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality\nand pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which\ncould make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-\nH7N9 drug. In this study, we used the general H7N9 neuraminidase and oseltamivir-resistant influenza virus neuraminidase as the\nacceptors and employed the small molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as the donors to\nperform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. The results\nshowed that quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir-comparable high binding potentials with\nneuraminidase. Further analyses showed that R294K mutation in neuraminidase could remarkably decrease the binding energies\nfor oseltamivir, while other small molecules showed stable binding abilities with mutated neuraminidase. Taken together, the\nmolecular docking studies identified four potential inhibitors for neuraminidase of H7N9, which might be effective for the drugresistant\nmutants....
The class of 3-{4-(5-mercapto-1,3,4-oxadiazole-2-yl) phenylimino} indolin-2-one is still not very well understood. This category shows potential in several classes of drugs. We have exploited the nucleus for potential anticancer agents. As anticancer drugs on the various site of the cell cycle, interfering with DNA structure, inhibiting cell wall etc. but basically it should bind to the site of DNA molecule to get the promising anticancer activity. We have undertaken the molecular docking study of isatin derivatives so as to explore this moiety and get novel anticancer agents. Molecular docking study gives binding sites, molecular interpretation and structural analysis of the compound that will help us to design new promising set of compounds which will help to design novel anticancer agents....
Graphene, a two-dimensional nanomaterial with unique biomedical properties, has attracted great attention due to its potential\napplications in graphene-based drug delivery systems (DDS). In this work graphene sheets with various sizes and graphene oxide\nfunctionalized with polyethylene glycol (GO-PEG) are utilized as nanocarriers to load anticancer drug molecules including CE6,\nDOX, MTX, and SN38.We carried out molecular dynamics calculations to explore the energetic stabilities and diffusion behaviors\nof the complex systems with focuses on the effects of the sizes and functionalization of graphene sheets as well as the number\nand types of drug molecules. Our study shows that the binding of graphene-drug complex is favorable when the drug molecules\nand finite graphene sheets become comparable in sizes. The boundaries of finite sized graphene sheets restrict the movement\nof drug molecules. The double-side loading often slows down the diffusion of drug molecules compared with the single-side\nloading. The drug molecules bind more strongly with GO-PEG than with pristine graphene sheets, demonstrating the advantages\nof functionalization in improving the stability and biocompatibility of graphene-based DDS....
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