Synthesis, anticancer activity and molecular docking studies on 1,2-diarylbenzimidazole analogues as anti-tubulin agents

Bioorg Chem. 2019 Nov:92:103219. doi: 10.1016/j.bioorg.2019.103219. Epub 2019 Aug 26.

Abstract

Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI50 = 0.71-2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC50 > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC50 = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.

Keywords: Apoptosis; Benzimidazole; Cell cycle arrest; Molecular docking; Tubulin inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Polymerization / drug effects
  • Quantitative Structure-Activity Relationship
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / metabolism
  • Tubulin / metabolism*
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Reactive Oxygen Species
  • Tubulin
  • Tubulin Modulators
  • benzimidazole