Synthesis, biological evaluation and molecular docking of 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives as potential Staphylococcus aureus Sortase A inhibitors

被引：19

作者：

Zhang, Yong ^{[1
]}

Bao, Jian ^{[2
]}

Deng, Xin-Xian ^{[2
]}

He, Wan ^{[2
]}

Fan, Jia-Jun ^{[2
]}

Jiang, Fa-Qin ^{[2
]}

Fu, Lei ^{[2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, 800 Dongchuan Rd, Shanghai 200240, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd, Shanghai 200240, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 16期

关键词：

Sortase A; Anti-infective; Benzo[d] oxazole; TRANSPEPTIDASE; TARGET;

D O I：

10.1016/j.bmcl.2016.06.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives were designed, synthesized and evaluated for their in vitro inhibitory activities against Staphylococcus aureus Sortase A with known Sortase A inhibitor pHMB as positive compound (IC50 = 130 mu M). Most compounds exhibited excellent inhibitory activity (IC50 = 19.8-184.2 mu M). Structure-activity relationship studies demonstrated that substitution at 7-position and 2-position of benzoxazole had great influence on the activities. Specifically, the substituent at 7-position is indispensable for inhibitory activity. The molecular docking studies revealed the i-butyl amide group went towards the beta 6/beta 7 loop-beta 8 substructure of the protein and the benzoxazole core lied in a hydrophobic pocket composed of Ala118, Val166, Val168, Val169 and Ile182, shaping the whole molecule into a L-shape mode to be recognized by Sortase A. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4081 / 4085

页数：5

共 16 条

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