In Vitro and In Silico Evaluations of Anti-Mycobacterium tuberculosis Activity of Benzohydrazones Compounds

Tuberculosis is a disease caused by Mycobacterium tuberculosis , with high mortality rates and an extended treatment that causes severe adverse effects, besides the emergence of resistant bacteria. Therefore, the search for new compounds with anti- M. tuberculosis activity has considerably increased in recent years. In this context, benzohydrazones are significant compounds that have antifungal and antibacterial action. This study aimed at evaluating the in vitro activity of 18 benzohydrazones against M. tuberculosis . Compounds' cytotoxicity, inhibition of M. tuberculosis efflux pumps, and in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) assays were also performed. In general, the minimum inhibitory concentration values for the standard M. tuberculosis H 37 Rv strain ranged from 7.8 to 250 μg/mL, and some compounds were not toxic to any of the cells tested (IC 50 ranged from 18.0 to 302.5 μg/mL). In addition, compounds ( 4 ) and ( 7 ) showed to be possible efflux pump inhibitors. In ADMET assays, all benzohydrazones had high gastrointestinal absorption. Most of the compounds were able to overcome the blood–brain barrier, and no compounds had irritant or tumorigenic effects. Compounds ( 1 ), ( 3 ), ( 9 ), ( 12 ), and ( 15 ) stood out for showing good activities, both in vitro and in silico assays.