Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

The natural product withaferin A exhibits potent antitumor activity and Other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure-activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different Cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A.

DRO81-1; Withalongolide A; jaborosalactone; macrocycle; triacetate; withaferin A.