Structure-activity relationship studies of [1,2,5]oxadiazolo[3,4-b]pyrazine-containing polymyxin-selective resistance-modifying agents.
Somnath Dutta, Nianzi Liu, Yuefeng Gao, Lily Beck, Xiang Wang
Author Information
Somnath Dutta: Department of Chemistry, University of Colorado, Boulder, CO 80309, USA.
Nianzi Liu: Department of Chemistry, University of Colorado, Boulder, CO 80309, USA.
Yuefeng Gao: Department of Chemistry, University of Colorado, Boulder, CO 80309, USA.
Lily Beck: Department of Chemistry, University of Colorado, Boulder, CO 80309, USA.
Xiang Wang: Department of Chemistry, University of Colorado, Boulder, CO 80309, USA. Electronic address: xiang.wang@colorado.edu.
Multidrug-resistant (MDR) Gram-negative bacteria are an urgent and rapidly spreading threat to human health with limited treatment options. Previously, we discovered a novel [1,2,5]oxadiazolo[3,4-b]pyrazine-containing compound (1) that selectively re-sensitized a variety of MDR Gram-negative bacteria to colistin, one of the last-resort antibiotic. Herein, we report the structure-activity relationship studies of compound 1 that led to the discovery of several more potent and/or less toxic resistance-modifying agents (RMAs). Further evaluation of these RMAs showed that they were effective in a wide range of MDR bacteria. These results demonstrated these compounds as a novel class of RMAs and may be further developed as therapeutic agents.
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R33 AI121581/NIAID NIH HHS
Anti-Bacterial Agents
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria
Gram-Negative Bacterial Infections
Humans
Microbial Sensitivity Tests
Polymyxins
Pyrazines
Structure-Activity Relationship
Anti-Bacterial Agents
Polymyxins
Pyrazines
