Current Issue : April - June Volume : 2016 Issue Number : 2 Articles : 5 Articles
Histone deacetylases (HDAC) are metal-dependent enzymes and considered as important targets\nfor cell functioning. Particularly, higher expression of class I HDACs is common in the\nonset of multiple malignancies which results in deregulation of many target genes involved in\ncell growth, differentiation and survival. Although substantial attempts have been made to control\nthe irregular functioning of HDACs by employing various inhibitors with high sensitivity\ntowards transformed cells, limited success has been achieved in epigenetic cancer therapy.\nHere in this study, we used ligand-based pharmacophore and 2-dimensional quantitative structure\nactivity relationship (QSAR) modeling approaches for targeting class I HDAC isoforms.\nPharmacophore models were generated by taking into account the known IC50 values and\nexperimental energy scores with extensive validations. The QSAR model having an external\nR2 value of 0.93 was employed for virtual screening of compound libraries. 10 potential lead\ncompounds (C1-C10) were short-listed having strong binding affinities for HDACs, out of which\n2 compounds (C8 and C9) were able to interact with all members of class I HDACs. The potential\nbinding modes of HDAC2 and HDAC8 to C8 were explored through molecular dynamics\nsimulations. Overall, bioactivity and ligand efficiency (binding energy/non-hydrogen atoms)\nprofiles suggested that proposed hits may be more effective inhibitors for cancer therapy....
Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis\nin preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds\nlike flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were\nperformed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab.\nHowever, this data requires in vitro and in vivo verification for further consideration....
Molecular docking simulation of catechin and its derivatives on Glucosamine-6-\nPhosphate Synthase (GlmS) has been performed in this research. GlmS inhibition by a\nparticular ligand will suppress the production of bacterial cell wall and significantly reduce the\npopulation of invading bacteria. In this study, catechin derivatives i.e epicatechin, galloatechin\nand epigalloatechin were found to have stronger binding affinities as compared to natural\nligand of GlmS, Fructose-6-Phosphate (F6P). Those three ligands were docked on the same\npocket in GlmS target as F6P, with 70% binding sites similarity. Based on the docking results,\ngallocatechin turns out to be the most potent ligand for anti-bacterial agent with Ã?â?G= -8.00\nkcal/mol. The docking between GlmS and catechin derivatives are characterized by a constant\npresent of a strong hydrogen bond between functional group O3 and Ser-349. This hydrogen\nbond most likely plays a significant role in the docking mechanism and binding modes\nselection. The surprising result is catechin itself exhibited a quite strong binding with GlmS\n(Ã?â?G= -7.80 kcal.mol), but docked on a completely different pocket compared to other ligands.\nThis results suggest that catechin might still have a curing effect but with a completely\ndifferent pathway and mechanism as compared to its derivatives....
In silico technique was applied to screen potential of 16 compounds of 5,5-dimethylthiohydantoin\nderivatives as androgen antagonist. The 3D structure of the protein was obtained from PDB database.\nDocking analysis of the compounds was performed using hex docking. Molecular modeling\nanalysis exhibits relatively low LUMO-HOMO energy gap of the studied molecules, indicating that\nit would be kinetically stable. None of the compounds violated Lipinski�s parameters, making them\npotentially promising agents for biological activities. The title compounds exhibited the lowest\ndocking energy of protein-ligand complex. Finally, the results indicate that these compounds are\npotentially as an androgen antagonist, and expected to be effective in prostate cancer treatment....
Anticoagulants are attractive drugs for the treatment of various disorders and in combination of some cardiovascular drugs. In the present work, 3D quantitative structure-activity relationship studies were conducted on a series of anticoagulants. Significant correlation coefficients (r2 =0.8811, q2 =0.8187; r2 =0.9197 and q2 =0.7975) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the potency of an external test set and the predicted values obtained from the 3D models were in good agreement with the experimental results. The final QSAR models along with the information obtained from 3D steric and electrostatic contour maps will be useful for the design of anticoagulants having improved potency....
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