Ring A structural modified derivatives of withaferin A and the evaluation of their cytotoxic potential.

ABSTRACT

Regio-/stereoselective Michael addition to ring A of withaferin-A was performed using an optimized reaction procedure to synthesise a library of 2,3-dihydro,3-ß-substituted withaferin-A derivatives. The analogues thus obtained were evaluated for in vitro cytotoxicity against various human cancer cell lines. 3-Azido analogue exhibited 35-fold increase (IC(50)=0.02-1.9 µM) in cytotoxicity against almost the entire cell lines tested when compared to the parent molecule. However, further modifications of 3-azido analogue with various alkynes under Husigen's cycloaddition conditions generated a variety of triazole derivatives with reduced cytotoxicity.