Synthesis and structure-activity relationship study of novel quinazolinone-based inhibitors of MurA

被引：52

作者：

Hrast, Martina ^{[1
]}

Rozman, Kaja ^{[1
]}

Jukic, Marko ^{[1
]}

Patin, Delphine ^{[2
]}

Gobec, Stanislav ^{[1
]}

Sova, Matej ^{[1
]}

机构：

[1] Univ Ljubljana, Fac Pharm, Askerceva 7, SI-1000 Ljubljana, Slovenia

[2] Univ Paris Saclay, Univ Paris Sud, Bacterial Cell Envelopes & Antibiot Grp, I2BC,CEA,CNRS, F-91198 Gif Sur Yvette, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 15期

关键词：

Peptidoglycan; MurA enzyme; Antibacterial agents; Quinazolinones; PEPTIDOGLYCAN BIOSYNTHESIS; DISCOVERY; DOCKING;

D O I：

10.1016/j.bmcl.2017.05.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

MurA is an intracellular bacterial enzyme that is essential for peptidoglycan biosynthesis, and is therefore an important target for antibacterial drug discovery. We report the synthesis, in silico studies and extensive structure-activity relationships of a series of quinazolinone-based inhibitors of MurA from Escherichia coli. 3-Benzyloxyphenylquinazolinones showed promising inhibitory potencies against MurA, in the low micromolar range, with an IC50 of 8 mu M for the most potent derivative (58). Furthermore, furan-substituted quinazolinones (38, 46) showed promising antibacterial activities, with MICs from 1 mu g/mL to 8 mu g/mL, concomitant with their MurA inhibitory potencies. These data represent an important step towards the development of novel antimicrobial agents to combat increasing bacterial resistance. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3529 / 3533

页数：5

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