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  • Title: The Discovery of 2-Aminobenzimidazoles That Sensitize Mycobacterium smegmatis and M. tuberculosis to β-Lactam Antibiotics in a Pattern Distinct from β-Lactamase Inhibitors.
    Author: Nguyen TV, Blackledge MS, Lindsey EA, Minrovic BM, Ackart DF, Jeon AB, Obregón-Henao A, Melander RJ, Basaraba RJ, Melander C.
    Journal: Angew Chem Int Ed Engl; 2017 Mar 27; 56(14):3940-3944. PubMed ID: 28247991.
    Abstract:
    A library of 2-aminobenzimidazole derivatives was screened for the ability to suppress β-lactam resistance in Mycobacterium smegmatis. Several non-bactericidal compounds were identified that reversed intrinsic resistance to β-lactam antibiotics in a manner distinct from β-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 β-lactamase inhibitors.
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