Discovery of non-peptide inhibitors of Plasmepsin II by structure-based virtual screening

被引：11

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 07期

基金：

中国国家自然科学基金;

关键词：

Plasmepsin II; Anti-malaria; Virtual screening; Molecular docking; PLASMODIUM-FALCIPARUM; ASPARTIC PROTEASES; SUBSTITUTED PIPERIDINES; POTENT INHIBITORS; RENIN INHIBITORS; DESIGN; RESISTANCE; ENZYME;

D O I：

10.1016/j.bmcl.2013.01.128

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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.

引用

页码：2078 / 2082

页数：5

共 31 条

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