Introduction:
As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin
(DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity
(>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into
various derivatives and study their antitubercular potential.
Materials and Methods:
DHA-1 was semi-synthetically converted into four new acyl derivatives
(DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium
tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5
µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the
pathogen.
Results:
In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting
the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008
cells and Mouse bone marrow derived macrophages.
Conclusion:
DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection
model. To the best of our knowledge, this is the first-ever report on the antitubercular potential
of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial
drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive,
and non-toxic natural product.