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Structure-based and ligand-based drug design for microsomal prostaglandin E synthase-1 inhibitors

Authors :
Chun Lin Lee
Mao-Feng Sun
Calvin Yu-Chian Chen
Chia Ling Li
Mark Fisher
Hsin Yi Chen
Tung Ti Chang
Yung Hao Wong
Wen Chang Fang
Fuu Jen Tsai
Source :
Molecular Simulation. 37:226-236
Publication Year :
2011
Publisher :
Informa UK Limited, 2011.

Abstract

Microsomal prostaglandin E synthase-1 (mPGES-1) has been regarded as an attractive drug for inflammation-related diseases. In search of new mPGES-1 inhibitors, we performed virtual screening using our traditional Chinese medicine and natural products database (http://tcm.cmu.edu.tw/) and constructed comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) using a training set of 30 experimentally tested mPGES-1 inhibitors. The CoMFA and CoMSIA models derived were statistically significant with cross-validated coefficient values of 0.808 for CoMFA and 0.829 for CoMSIA and non-cross-validated coefficient values of 0.829 for CoMFA and 0.980 for CoMSIA. Docking and de novo evolution design gave three top derivatives, 2-O-caffeoyl tartaric acid-Evo_2, glucogallin-Evo_1 and 3-O-feruloylquinic acid-Evo_7 that have higher binding affinities than the control, glutathione. These three derivatives have interactions with Arg70, Arg73, Arg110, Arg126 and Arg38, which ...

Details

ISSN :
10290435 and 08927022
Volume :
37
Database :
OpenAIRE
Journal :
Molecular Simulation
Accession number :
edsair.doi...........204528fbaffa7963b051cb993808a91b
Full Text :
https://doi.org/10.1080/08927022.2010.538054