Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies

Molecular BioSystems
Md Ataul Islam, Tahir S Pillay

Abstract

Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease which is a collection of symptoms and infections caused by a retrovirus, human immunodeficiency virus (HIV). There is currently no curative treatment and therapy is reliant on the use of existing anti-retroviral drugs. Pharmacoinformatics approaches have already proven their pivotal role in the pharmaceutical industry for lead identification and optimization. In the current study, we analysed the binding preferences and inhibitory activity of HIV-integrase inhibitors using pharmacoinformatics. A set of 30 compounds were selected as the training set of a total 540 molecules for pharmacophore model generation. The final model was validated by statistical parameters and further used for virtual screening. The best mapped model (R = 0.940, RMSD = 2.847, Q(2) = 0.912, se = 0.498, Rpred(2) = 0.847 and rm(test)(2) = 0.636) explained that two hydrogen bond acceptor and one aromatic ring features were crucial for the inhibition of HIV-integrase. From virtual screening, initial hits were sorted using a number of parameters and finally two compounds were proposed as promising HIV-integrase inhibitors. Drug-likeness properties of the final screened compounds were compa...Continue Reading

References

May 1, 1997·Trends in Biotechnology·M Thomas, L Brady
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y GoldgurD R Davies
Mar 10, 2000·Biochimica Et Biophysica Acta·A G Tomasselli, R L Heinrikson
Jul 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·J C ChenR M Stroud
Feb 23, 2002·Journal of Molecular Graphics & Modelling·Alexander Golbraikh, Alexander Tropsha
May 31, 2002·Journal of Medicinal Chemistry·Daniel F VeberKenneth D Kopple
Jul 23, 2003·Current Pharmaceutical Design·John H van Drie
Oct 3, 2003·Chemistry & Biology·Amy C Anderson
Apr 6, 2005·Journal of Chemical Information and Modeling·Rajendra KristamDavid Thorner
Apr 27, 2005·Annals of Neurology·Jennifer E CookWilliam R Tyor
Mar 3, 2007·Journal of Chemical Information and Modeling·Jing WeiQingzhi Gao
Apr 28, 2007·AIDS Patient Care and STDs
May 28, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Partha Pratim RoyKunal Roy
Jul 2, 2009·Expert Opinion on Drug Delivery·Kavitha S RaoVinod Labhasetwar
Mar 3, 2010·Journal of Molecular Modeling·Indrani MitraKunal Roy
Mar 9, 2010·European Journal of Medicinal Chemistry·Sugunadevi SakkiahKeun Woo Lee
Jun 28, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Karnati Konda ReddyChandrabose Selvaraj
Dec 14, 2011·Expert Opinion on Pharmacotherapy·Maxwell O AkanbiRobert L Murphy
Dec 29, 2011·Journal of Chemical Information and Modeling·Kunal RoyHumayun Kabir
Feb 9, 2012·Medicinal Chemistry·Shikha KaushikZaihra Anwar
Apr 28, 2012·Bioinformatics·Adrià Cereto-MassaguéSantiago Garcia-Vallvé
Jan 5, 2013·Current Computer-aided Drug Design·Pawan GuptaNilanjan Roy
Jul 20, 2014·JAMA : the Journal of the American Medical Association

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