RELATIONSHIP BETWEEN CHEMICAL STRUCTURE AND ANTITUMOR ACTIVITY OF WITHAFERIN A ANALOGUES

Abstract

The relationship between chemical structure and antitumor activity of AB ring analogues of withaferin A was examined by cell growth inhibition in mouse leukemia L5178Y cells in vitro. The 5, 6β-epoxy-4β-ol (5) and 5, 6α-epoxy-4α-ol (6) with 1-keto-2-ene function and cholesterol side chain have antitumor activity. The 4, 5-epoxy-6-hydroxyl compounds (9-16) were found to be equally or more active than corresponding 5, 6-epoxy-4-hydroxyl analogues. The antitumor activities of the 4, 5-epoxides paralleled the reactivities in ring opening reaction with acid. For the antitumor activity of withanolides, the unsaturated lactone in the side chain is important, and 1-keto-2-ene and epoxide functions were essential to elicit the activity.