Combined 3D-QSAR modeling and molecular docking study on indolinone derivatives as inhibitors of 3-phosphoinositide-dependent protein kinase-1

Journal of Chemical Information and Modeling
Mohamed Diwan M AbdulHameedChang-Guo Zhan

Abstract

3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs. In order to understand the structure-activity correlation of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The study has resulted in two types of satisfactory 3D-QSAR models, including the CoMFA model (r(2)=0.907; q(2)=0.737) and CoMSIA model (r(2)=0.991; q(2)=0.824), for predicting the biological activity of new compounds. The detailed microscopic structures of PDK1 binding with inhibitors have been studied by molecular docking. We have also developed docking-based 3D-QSAR models (CoMFA with q(2)=0.729; CoMSIA with q(2)=0.79). The contour maps obtained from the 3D-QSAR models in combination with the docked binding structures help to better interpret the structure-activity relationship. All of the structural insights obtained from both the 3D-QSAR contour maps and molecular docking are consistent with the available experimental activity data. This is the first report on 3D-QSAR modeling of PDK1 inhibitors. The satisfactory results strongly suggest that the developed 3D-QSAR models and the...Continue Reading

References

Jun 1, 1995·Ecotoxicology and Environmental Safety·F BriensM Robba
Oct 1, 1993·Journal of Computer-aided Molecular Design·B L Bush, R B Nachbar
Aug 23, 1996·Journal of Molecular Biology·M RareyG Klebe
Feb 1, 1996·Journal of Computer-aided Molecular Design·M RareyT Lengauer
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Nov 1, 2000·Cell·A Toker, A C Newton
Apr 12, 2001·Journal of Medicinal Chemistry·M Stahl, M Rarey
Jun 8, 2001·Journal of Computer-aided Molecular Design·T J EwingI D Kuntz
Jul 12, 2002·The EMBO Journal·Margaret A LawlorDario R Alessi
Oct 9, 2002·Mini Reviews in Medicinal Chemistry·A K Debnath
Jan 25, 2003·Journal of Molecular Graphics & Modelling·Jonas BoströmJohan Gottfries
Feb 13, 2003·Biopolymers·Mark R McGannFrank K Brown
Aug 30, 2003·American Journal of Surgery·Julian A Kim
May 26, 2004·Bioorganic & Medicinal Chemistry·Gilberto M Sperandio da SilvaEliezer J Barreiro
Jun 24, 2004·Seminars in Cell & Developmental Biology·Alfonso MoraDario R Alessi
Mar 18, 2005·The Journal of Biological Chemistry·Richard I FeldmanDamian O Arnaiz
Oct 26, 2005·Current Biology : CB·Jose R BayascasDario R Alessi
Feb 9, 2006·Nature Biotechnology·Ken Garber
Apr 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Qing ZhangJennifer Rubin Grandis
Jul 14, 2006·Bioorganic & Medicinal Chemistry·Aihua XieRobert J Doerksen
Dec 22, 2006·The Journal of Physical Chemistry. B·Mohamed Diwan M AbdulhameedChang-Guo Zhan
Jan 27, 2007·Journal of Computer-aided Molecular Design·Richard D Cramer, Bernd Wendt
May 29, 2007·Bioorganic & Medicinal Chemistry Letters·Imadul IslamDamian O Arnaiz
Jun 5, 2007·Bioorganic & Medicinal Chemistry Letters·Imadul IslamDamian O Arnaiz
Dec 7, 2007·Journal of Chemical Information and Modeling·Mohamed Diwan M AbdulHameedChang-Guo Zhan
Feb 22, 2008·Journal of Medicinal Chemistry·Alex M AronovMark A Murcko
Aug 1, 1988·Journal of the American Chemical Society·R D CramerJ D Bunce

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Citations

Jun 15, 2013·Molecular BioSystems·Jinghui WangLing Yang
Jan 1, 2012·International Journal of Medicinal Chemistry·Naoyuki AsakawaNoriaki Hirayama
Sep 29, 2011·International Journal of Molecular Sciences·Yuanxin TianShuguang Wu
Oct 22, 2011·International Journal of Molecular Sciences·Meng-Qi ZhangChun-Zhi Ai
Jan 25, 2012·International Journal of Molecular Sciences·Pingping BaoLing Yang
Jan 23, 2016·International Journal of Molecular Sciences·Yinfeng YangLing Yang
Jun 25, 2019·Journal of Biomolecular Structure & Dynamics·Wenya Han, Jiazhong Li
Oct 12, 2018·Anti-cancer Agents in Medicinal Chemistry·Rabia HameedShagufta Perveen

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