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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:
Ethical conduct of research
The use of mice for infectious studies (IAEC/201/42A dated 15 April 2015) was approved by Institutional Animal Ethics Committee.
Financial & competing interests disclosure
This work is supported by CSIR-CDRI's intramural funds. This manuscript bears CSIR-CDRI communication number 9529. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/fmb-2017-0054.