Abstract
Our objective was to identify a more potent curcumin derivative with specific activity against Mycobacterium tuberculosis. A total of21 curcumin derivatives were synthesized and detailed bio-evaluation was carried out including determination of static/cidality, synergy with front-line antituberculosis drugs and determination of efficacy in the murine model of M. tuberculosis infection. We identified CPMD-6d dihydrochloride exhibiting concentration-dependent bactericidal activity against M. tuberculosis (MIC 2μg/ml), even against drug-resistant strains. In addition, it synergizes with front-line antituberculosis drugs as well as significantly reduces bacterial load in mice lungs and spleen at 25mg/kg as compared with ethambutol at 100mg/kg. Taken together, CPMD-6d dihydrochloride exhibits all properties to be positioned as a novel molecule of interest for treatment of tuberculosis. Graphical abstract: [Formula: see text].
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