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. , ...Daha Fazla

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.22, sa.12, ss.3096-3104, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Konu: 12
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.bmc.2014.04.027
  • Sayfa Sayıları: ss.3096-3104


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.