Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3877-81. doi: 10.1016/j.bmcl.2014.06.050. Epub 2014 Jun 26.

Abstract

A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 μM and 1.06 to 12.89 μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.

Keywords: Anticancer; Apoptosis; Benzimidazole; Cell cycle arrest; Pyrimidine.

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 Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Pyrimidines
  • pyrimidine