Comparative molecular field analysis of a series of paclitaxel analogues

Journal of Medicinal Chemistry
Q ZhuF Chu

Abstract

A series of 94 paclitaxel analogues exhibiting antitumor activity by promoting the assembly of microtubules and inhibiting the disassembly process of microtubules to tubulin were investigated using the comparative molecular field analysis (CoMFA) method. These compounds belonging to 10 structural classes were randomly divided into a training set of 80 compounds and a test set of 14 compounds. Since the three-dimension structure of ligand--receptor complex is unknown, from X-ray and NMR data we rationally selected the three-dimension structure of paclitaxel in a polar solution as the active conformation and starting structure for molecule modeling, the other molecules were aligned using this molecule model as the template. The most optimal CoMFA yielded a two-components model, with significant cross-validation r2cv of 0.640 and conventional r2 of 0.868. The predictive ability of training set model was tested on the test set of 14 compounds. The tests not only revealed the robustness of the CoMFA model but demonstrated that for our model r2pred based on the mean activity of test set compounds can accurately estimate external predictivity but r2pred based on the mean activity of training set compounds overestimated the model. The ...Continue Reading

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Citations

Jul 17, 2012·Cancer Letters·Lan Feng, Russell J Mumper
Nov 26, 1999·Bioorganic & Medicinal Chemistry Letters·T C BogeG I Georg
Oct 19, 2013·Bioconjugate Chemistry·Simona MuraPatrick Couvreur
May 26, 2016·International Journal of Molecular Sciences·Ziyuan MengGe Zhang
Feb 6, 2019·Journal of Drug Targeting·Simona MuraJulien Nicolas
Jan 8, 2013·Journal of Chemical Theory and Computation·Giorgio MaccariMaurizio Botta

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