Synthesis and In Vitro Biological Activity Evaluation of the Derivatives of Combretastatin A-4

Combretastatin A-4 (CA-4) is a potent anti-tumor agent, which strongly inhibits tubulin polymerization. A common problem is the inactivation of derivatives with cis-configurated ethylene bridges during storage. β-Lactam analogs of CA-4 were synthesized in order to avoid isomerization to E-forms. Moreover, B-ring modifications (3,4,5-trimethoxyphenyl ring, furan ring) were studied with regard to biological activity. Their cytotoxic effects were evaluated in vitro against L1210 leukemia cell. The derivatives might provide some rational basis for further optimal structural modification.