Relationship between chemical structure and antitumor activity of withaferin A analogues.

Publisher Website
Google Scholar
Abstract
The relationship between chemical structure and antitumor activity of AB ring analogs of withaferin A was examined by cell growth inhibition in mouse leukemia L5178Y cells in vitro. The 5, 6.beta.-epoxy-4.beta.-ol (5) and 5,6.alpha.-epoxy-4.alpha.-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 equally or more active than corresponding 5,6-epoxy-4-hydroxyl analogs. 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.