Dihydroartemisinin and its Analogs: A New Class of Antitubercular Agents

Author(s): Komal Kalani, Vinita Chaturvedi, Priyanka Trivedi, Sudeep Tondon, Santosh Kumar Srivastava*

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 8 , 2019

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Graphical Abstract:


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.

Methods: 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.

Keywords: Dihydroartemisinin, Semi-synthetic derivatives, Anti-tubercular activity, Synergistic effect Artemisia annua, Tuberculosis.

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Article Details

Year: 2019
Published on: 04 March, 2019
Page: [594 - 599]
Pages: 6
DOI: 10.2174/1568026619666190304142802
Price: $65

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