Komal Kalani, Vineeta Chaturvedi, Priyanka Trivedi, Sudeep Tondon and Santosh Kumar Srivastava* Pages 1 - 6 ( 6 )
Background: Tuberculosis is one of the leading causes of mortality worldwide. Resistance against the frontline anti-tubercular drugs has worsened the already alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-tubercular agents possessing novel modes of action.
Objective: Chemical transformation of dihydroartemisinin for anti-tubercular lead optimization. Method: Dihydroartemisinin, a metabolite of artemisinin was chemically converted into eight acyl derivatives and were evaluated for anti-tubercular potential against H37Rv virulent strain of Mycobacterium tuberculosis by agar-based proportion assay. Further, synergistic activity of 12-O-m-anisoyl dihydroartemisinin was also studied with the front-line anti-TB drugs, isoniazid and rifampicin.
Results: The results showed that all the derivatives were active but out of eight, 12-O-m-anisoyl dihydroartemisinin and 12-O-p-anisoyl dihydroartemisinin were significantly active (MIC 25.0 μg/mL). In synergistic activity evaluation, the 12-O-m-anisoyl dihydroartemisinin derivative showed reduction in MIC (by 1/8th, i.e. 3.12 μg/mL and that of rifampicin by ¼th, i.e. 0.05 μg/mL) with the front-line anti-TB drug, rifampicin. The sumfractional inhibitory concentration (Σ FIC) was 0.375.
Conclusion: These results suggested a synergistic effect of the 12-O-m-anisoyl dihydroartemisinin with rifampicin and established its base for the development of anti-tubercular agents from an in-expensive and non-toxic natural product. To the best of our knowledge this is the first ever report on the anti-tubercular potential of dihydroartemisinin and its derivatives.
Dihydroartemisinin, semi-synthetic derivatives, anti-tubercular activity, synergistic effect.
Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Microbiology Division, Central Drug Research Institute, Lucknow, Microbiology Division, Central Drug Research Institute, Lucknow, Process Chemistry & Chemical Engineering Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow