Biological evaluation of novel curcumin–pyrazole–mannich derivative active against drug-resistant Mycobacterium tuberculosis. (November 2017)

• Record Type: Journal Article
• Authors: Singh, Alok Kumar; Yadav, Pragya; Karaulia, Pratiksha; Singh, Vinay Kumar; Gupta, Pushpa; Puttrevu, Santosh Kumar; Chauhan, Sanjay; Bhatta, Rabi S; Tadigoppula, Narender; Gupta, Umesh D; Chopra, Sidharth; Dasgupta, Arunava
• Is Part Of: Future microbiology. Volume 12:Number 15(2017)
• Page Start: 1349
• Page End: 1362
• Publication Date: 2017-11
• Subjects: antibiotics -- curcumin -- drug resistance -- Mycobacterium tuberculosis -- pyrazole; Microbiology -- Research -- Periodicals; 616.9041
• DOI: 10.2217/fmb-2017-0054
• Languages: English
• ISSNs: 1746-0913

Abstract

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: