Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents

Bioorg Chem. 2015 Dec:63:72-84. doi: 10.1016/j.bioorg.2015.09.003. Epub 2015 Oct 8.

Abstract

A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results suggested that these conjugates inhibit tubulin polymerization with IC50 values 1.12 and 1.59μM respectively. Immunofluorescence analysis also suggested that these conjugates effectively inhibited the microtubule assembly in MCF-7 cells. Further, molecular docking studies indicated that these conjugates 5c and 5p interact and binds efficiently with the tubulin protein. By and large, the results demonstrated that these benzimidazole-oxindole conjugates possess cytotoxic property by inhibiting the tubulin polymerization.

Keywords: Benzimidazoles-oxindoles; Cell cycle; Cytotoxic activity; Docking; Tubulin polymerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Models, Molecular
  • Molecular Structure
  • Oxindoles
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Indoles
  • Oxindoles
  • Tubulin
  • 2-oxindole
  • benzimidazole