In vitro antimycobacterial activity of 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione: a new chemical entity against Mycobacterium tuberculosis

Abstract

This study reports on the in vitro antituberculosis potential of 2-(((2-hydroxyphenyl) amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD) against Mycobacterium tuberculosis H37Rv. PAMCHD has been proven to be a tuberculostatic as well as a tuberculocidal agent by agar and broth dilution methods with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values equivalent to some standard antituberculosis drugs (ATDs). The dynamics of M. tuberculosis killing revealed the time- as well as concentration-dependent antituberculosis activity of PAMCHD and it sterilized M. tuberculosis culture at or above 10.0 µg/mL. PAMCHD acts either synergistically or additively with ATDs. Isoniazid (INH) and PAMCHD post-antibiotic effects increased with concentration from 16.18 ± 13.30 and 31.64 ± 13.30 to 127.9 ± 27.60 and 138.71 ± 16.42 h, respectively, from 1 × MIC to 8 × MIC; no significant difference was observed between INH and PAMCHD post-antibiotic effects. M. tuberculosis mutation frequency against PAMCHD is lower than that of INH. Mutant prevention concentration (MPC) of INH, rifampin (RIF) and PAMCHD were observed to be 40, 160 and 160 µg/mL, respectively, and their MPC/MIC values were 128, 2051 and 64, respectively; this lowest MPC/MIC highlights the advantage of PAMCHD over RIF and INH.