Comparative Molecular Field Analysis and Molecular Docking Studies on Quinolinone Derivatives Indicate Potential Hepatitis C Virus Inhibitors.

Cell Biochemistry and Biophysics
Kullappan MalathiAnand Anbarasu

Abstract

Presently, there are no effective vaccines and anti-virals for the prevention and treatment of Hepatitis C virus infections and hence there is an urgent need to develop potent HCV inhibitors. In this study, we have carried out molecular docking, molecular dynamics and 3D-QSAR on heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone series using NS5B protein. Total of 41 quinolinone derivatives is used for molecular modeling study. The binding conformation and hydrogen bond interaction of the docked complexes were analyzed to model the inhibitors. We identified the molecule XXXV that had a higher affinity with NS5B. The molecular dynamics study confirmed the stability of the compound XXXV-NS5B complex. The developed CoMFA descriptors parameters, which were calculated using a test set of 13 compounds, were statistically significant. Our results will provide useful insights and lead to design potent anti-Hepatitis C virus molecules.

References

Aug 18, 2000·Seminars in Liver Disease·M Lechmann, T J Liang
Nov 20, 2003·Reviews in Medical Virology·Thomas Hügle, Andreas Cerny
Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Pierre L BeaulieuGeorge Kukolj
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Nov 9, 2004·Advances in Virus Research·Ralf BartenschlagerThomas Pietschmann
Mar 27, 2007·Transfusion·Naomi L C LubanHarvey J Alter
May 19, 2009·Journal of Clinical Gastroenterology·Andrew Aronsohn, Nancy Reau
Oct 3, 2009·Bioorganic & Medicinal Chemistry Letters·Iou-Jiun KangJyh-Haur Chern
Jan 6, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Paul FeuerstadtJohn F Reinus
Oct 21, 2010·Virologica Sinica·Susan L Uprichard
Jan 28, 2012·European Journal of Medicinal Chemistry·Daniel B NicholsNeerja Kaushik-Basu
Sep 25, 2012·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Daniel Lavanchy
Jan 1, 2011·Therapeutic Advances in Chronic Disease·Emilio Palumbo
Nov 2, 2013·Bioorganic & Medicinal Chemistry Letters·Timothy A StammersPierre L Beaulieu
Jan 15, 2014·European Journal of Medicinal Chemistry·Deepak K LokwaniDevanand B Shinde
May 30, 2014·Journal of Biomolecular Structure & Dynamics·Mahalakshmi ThillainayagamSudha Ramaiah
Dec 20, 2014·Cell Host & Microbe·Qiang DingAlexander Ploss
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl
May 25, 2016·Journal of Cellular Biochemistry·Subramanian SuganyaAnand Anbarasu

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Software Mentioned

CoMFA
Sybyl
GROMACS
PRODRG
ChemSketch
ACD
Surflex
dock

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