Design and synthesis of silicon-containing tubulin polymerization inhibitors: Replacement of the ethylene moiety of combretastatin A-4 with a silicon linker |
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Authors: | Masaharu Nakamura Daisuke Kajita Yotaro Matsumoto Yuichi Hashimoto |
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Affiliation: | Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan |
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Abstract: | 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. |
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Keywords: | Silicon Tubulin Combretastatin Colchicine Antitumor agent |
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