Silicon-containing combretastatin analogs were designed, synthesized and evaluated for stability and biological activities. Among them, compound 31 exhibited strong tubulin polymerization-inhibitory activity and very potent tumor cell growth-inhibitory activity (IC50 = 0.007 μM) in MCF-7 cell proliferation assay. This compound also potently inhibited [ 3H]colchicine binding (90.7% inhibition at 3 μM). These activities were comparable to those of combretastatin A-4 (CA-4) (1). In addition, compound 31 was physico-chemically more stable than 1. These results suggest that a silicon linker can act as a bioisoster of a cis carbon-carbon double bond.
- Antitumor agent