Dihydroartemisinin and its Analogs: A New Class of Antitubercular Agents
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.Journal Title:
Current Topics in Medicinal Chemistry