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

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16596

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题名:	Structure-based and ligand-based drug design for microsomal prostaglandin Esynthase-1 inhibitors
作者:	蔡輔仁;Tsai, Fuu-Jen;陳語謙;Chen, Calvin Yu-Chian
贡献者:	生物科技學系
关键词:	microsomal prostaglandin E synthase-1;QSAR;docking traditional Chinese medicine;database
日期:	2011-03
上传时间:	2012-11-23 09:14:56 (UTC+0)
摘要:	"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, glucogallinEvo_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 all are mPGES-1 key active site residues. In addition, these derivatives ﬁt well into the CoMFA and CoMSIA models, with hydrophobic, hydrophilic and electropositive substructures mapped onto corresponding contour plots. Hence, we suggest that these three de novo compounds could be a starting basis for new mPGES-1 inhibitors."
關聯:	MOLECULAR SIMULATION
显示于类别:	[生物科技學系] 期刊論文

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