文献类型：期刊文献

英文题名：Natural products as a gold mine for selective matrix metalloproteinases inhibitors

作者：Wang, Liyan[2];Li, Xi[2];Zhang, Shoude[1];Lu, Weiqiang[2];Liao, Sha[2];Liu, Xiaofeng[2];Shan, Lei[3];Shen, Xu[2];Jiang, Hualiang[2];Zhang, Weidong[1,3];Huang, Jin[2];Li, Honglin[2]

机构：[1]Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China;[3]Second Mil Med Univ, Dept Phytochem, Sch Pharm, Shanghai 200433, Peoples R China

年份：2012

卷号：20

期号：13

起止页码：4164

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000305279700024)】；

基金：This work was supported by the Innovation Program of Shanghai Municipal Education Commission (Grant 10ZZ41), the National Natural Science Foundation of China (Grants 21173076, 81102375 and 10979072), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grants 20090074120012 and 20110074120009), the 111 Project (Grant B07023), the Shanghai Committee of Science and Technology (Grants 11DZ2260600, 10431902600 and 09dZ1975700), the Fundamental Research Funds for the Central Universities, the 863 Hi-Tech Program of China (Grant 2012AA020308), the Special Fund for Major State Basic Research Project (Grant 2009CB918501), and the National S&T Major Project of China (Grant 2011ZX09307-002-03). H.L. is also sponsored by Shanghai Rising-Star Program (Grant 10QA1401800) and Program for New Century Excellent Talents in University (Grant NCET-10-0378). The MMP-1 expression plasmid was kindly provided by Professor Zigang Dong (University of Minnesota). The MMP-12 expression plasmid was kindly provided by Dr. Herbert Nar (Boehringer Ingelheim Pharma KG), The MMP-2 and MMP-9 plasmids were kindly provided by Dr. William G. Stetler-Stevenson (NCI, National Institutes of Health). The MMP-3 and MMP-13 plasmids were kindly provided by Professor Christopher M. Overall (University of British Columbia).

语种：英文

外文关键词：Matrix metalloproteinases; Virtual screening; Natural product; Anticancer agent

摘要：Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S10 pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.