文献类型：期刊文献

英文题名：Discovery of non-peptide inhibitors of Plasmepsin II by structure-based virtual screening

作者：Song, Yuwei[1];Jin, Huangtao[1];Liu, Xiaofeng[1];Zhu, Lili[1];Huang, Jin[1];Li, Honglin[1]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China

年份：2013

卷号：23

期号：7

起止页码：2078

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000316642900033)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants 21173076, 81102375, 81230090, 81222046 and 81230076), the Special Fund for Major State Basic Research Project (Grant 2009CB918501), the Shanghai Committee of Science and Technology (Grants 11DZ2260600 and 10431902600), and the 863 Hi-Tech Program of China (Grant 2012AA020308). Honglin Li is also sponsored by Program for New Century Excellent Talents in University (Grant NCET-10-0378).

语种：英文

外文关键词：Plasmepsin II; Anti-malaria; Virtual screening; Molecular docking

摘要：Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PM II from two chemical database. Five novel non-peptide inhibitors were identified and revealed moderate inhibitory potencies with IC50 ranged from 4.62 +/- 0.39 to 9.47 +/- 0.71 mu M. The detailed analysis of binding modes using docking simulations for five inhibitors showed that the inhibitors could be stabilized by forming multiple hydrogen bonds with catalytic residues (Asp 34 and Asp 214) and also with other key residues. (C) 2013 Elsevier Ltd. All rights reserved.