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.