Anthranilic amide and imidazobenzothiadiazole compounds disrupt Mycobacterium tuberculosis membrane potential.

ABSTRACT: A family of compounds typified by an anthranilic amide 1 was identified from a whole-cell screening effort targeted at identifying compounds that disrupt pH homeostasis in Mycobacterium tuberculosis. 1 demonstrated bactericidal activity against non-replicating M. tuberculosis in pH 4.5 buffer (MBC_4.5 = 6.3 μM). Exploration of the structure-activity relations failed to simplify the scaffold. The antitubercular activity proved dependent on the lipophilicity and planarity of the molecule and directly correlated with mammalian cytotoxicity. Further studies revealed a pH-dependent correlation between the family's disruption of M. tuberculosis membrane potential and antitubercular activity, with active compounds causing a drop in membrane potential a

SUBMITTER: Smith J 

PROVIDER: S-EPMC6596218 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature