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

Masaharu Nakamura, Daisuke Kajita, Yotaro Matsumoto, Yuichi Hashimoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7381-7391
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number23
DOIs
Publication statusPublished - 2013 Dec 1
Externally publishedYes

Keywords

  • Antitumor agent
  • Colchicine
  • Combretastatin
  • Silicon
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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