Consensus superiority of the pharmacophore-based alignment, over maximum common substructure (MCS): 3D-QSAR studies on carbamates as acetylcholinesterase inhibitors

Journal of Chemical Information and Modeling
Shailendra S ChaudhaeryAnil K Saxena

Abstract

In view of the nonavailability of complete X-ray structure of carbamates cocrystallized with AChE enzyme, the 3D-QSAR model development based on cocrystallized conformer (CCBA) as well as docked conformer-based alignment (DCBA) is not feasible. Therefore, the only two alternatives viz. pharmacophore and maximum common substructure-based alignments are left for the 3D-QSAR comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analyses (CoMSIA) model development. So, in the present study, the 3D-QSAR models have been developed using both alignment methods, where CoMFA and CoMSIA models based on pharmacophore-based alignment were in good agreement with each other and demonstrated significant superiority over MCS-based alignment in terms of leave-one-out (LOO) cross-validated q(2) values of 0.573 and 0.723 and the r(2) values of 0.972 and 0.950, respectively. The validation of the best CoMFA and CoMSIA models based on pharmacophore (Hip-Hop)-based alignment on a test set of 17 compounds provided significant predictive r(2) [r(2)(pred(test))] of 0.614 and 0.788, respectively. The contour map analyses revealed the relative importance of steric, electrostatic, and hydrophobicity for AChE inhibition ...Continue Reading

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Citations

Apr 26, 2011·Journal of Chemical Information and Modeling·Gonzalo Cerruela GarcíaMiguel Angel Gómez-Nieto
Jul 4, 2012·International Journal of Molecular Sciences·Liang OuyangMingli Xiang
Oct 30, 2014·Journal of Computer-aided Molecular Design·C David AnderssonAnna Linusson
Feb 2, 2019·Current Topics in Medicinal Chemistry·Mridula Saxena, Ragini Dubey
Jun 15, 2013·Molecular BioSystems·Jinghui WangLing Yang
Sep 12, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giuseppe FlorestaVincenzo Abbate
May 5, 2018·Journal of Receptor and Signal Transduction Research·Penghua LiZhiLi Zuo
Jan 1, 2021·Journal of Biomolecular Structure & Dynamics·Shibaji GhoshBishwajit Ganguly

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