Biological evaluation of novel curcumin-pyrazole-mannich derivative active against drug-resistant Mycobacterium tuberculosis.

AIM: Our objective was to identify a more potent curcumin derivative with specific activity against Mycobacterium tuberculosis.

MATERIALS &

METHODS

A total of 21 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.

RESULTS

We identified CPMD-6d dihydrochloride exhibiting concentration-dependent bactericidal activity against M. tuberculosis (MIC 2 μg/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 25 mg/kg as compared with ethambutol at 100 mg/kg.

CONCLUSION

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].