The Discovery of 2-Aminobenzimidazoles That Sensitize Mycobacterium smegmatis and M. tuberculosis to β-Lactam Antibiotics in a Pattern Distinct from β-Lactamase Inhibitors

被引：21

作者：

Nguyen, T. Vu ^{[1
]}

Blackledge, Meghan S. ^{[2
]}

Lindsey, Erick A. ^{[1
]}

Minrovic, Bradley M. ^{[1
]}

Ackart, David F. ^{[3
]}

Jeon, Albert B. ^{[3
]}

Obregon-Henao, Andres ^{[3
]}

Melander, Roberta J. ^{[1
]}

Basaraba, Randall J. ^{[3
]}

Melander, Christian ^{[1
]}

机构：

[1] North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA

[2] High Point Univ, Dept Chem, High Point, NC 27268 USA

[3] Colorado State Univ, Dept Microbiol, Dept Immunol, Dept Pathol, Ft Collins, CO 80523 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2017年 / 56卷 / 14期

关键词：

aminobenzimidazoles; antibiotic resistance; medicinal chemistry; tuberculosis; DRUG-RESISTANT TUBERCULOSIS; SMALL-MOLECULE SUPPRESSION; AUREUS;

D O I：

10.1002/anie.201612006

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A library of 2-aminobenzimidazole derivatives was screened for the ability to suppress beta-lactam resistance in Mycobacterium smegmatis. Several non-bactericidal compounds were identified that reversed intrinsic resistance to beta-lactam antibiotics in a manner distinct from beta-lactamase inhibitors. Activity also translates to M. tuberculosis, with a lead compound from this study potently suppressing carbenicillin resistance in multiple M. tuberculosis strains (including multidrug-resistant strains). Preliminary mechanistic studies revealed that the lead compounds act through a mechanism distinct from that of traditional beta-lactamase inhibitors.

引用

页码：3940 / 3944

页数：5

共 10 条

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