Design and synthesis of silicon-containing tubulin polymerization inhibitors: Replacement of the ethylene moiety of combretastatin A-4 with a silicon linker

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 mu M) in MCF-7 cell proliferation assay. This compound also potently inhibited [H-3]colchicine binding (90.7% inhibition at 3 mu M). 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. (C) 2013 Elsevier Ltd. All rights reserved.