Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities

Eur J Med Chem. 2014 Nov 24:87:306-15. doi: 10.1016/j.ejmech.2014.09.071. Epub 2014 Sep 28.

Abstract

A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin.

Keywords: Antiproliferative activity; Benzimidazole carbamates; Docking; Indole; Synthesis; Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / chemistry*
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Carbamates / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Humans
  • Models, Molecular
  • Protein Multimerization / drug effects
  • Protein Structure, Quaternary
  • Tubulin / chemistry
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Carbamates
  • Tubulin
  • Tubulin Modulators
  • benzimidazole