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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 12
  • Publication Date: 2014
  • Doi Number: 10.1016/j.bmc.2014.04.027
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • 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
  • Gazi University Affiliated: Yes


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.