Synthesis, biological evaluation and molecular docking studies of trans-indole-3-acrylamide derivatives, a new class of tubulin polymerization inhibitors

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BAYTAŞ S. , Inceler N., Yilmaz A., OLĞAÇ A. , Menevse S., BANOĞLU E. , ...More

BIOORGANIC & MEDICINAL CHEMISTRY, vol.22, no.12, pp.3096-3104, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 12
  • Publication Date: 2014
  • Doi Number: 10.1016/j.bmc.2014.04.027
  • Page Numbers: pp.3096-3104
  • Keywords: Synthesis, Anticancer activity, Indole, Tubulin polymerization, Colchicine binding, Apoptosis, Cell cycle arrest, Molecular docking, RAPID COLORIMETRIC ASSAY, ANTIMITOTIC AGENTS, CHALCONES, ANALOGS, COLCHICINE, GROWTH, CHEMISTRY, SURVIVAL, DESIGN, CELLS


In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC50 values of 9.5 and 5.1 mu M, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC50 = 17 mu M). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin. (C) 2014 Elsevier Ltd. All rights reserved.