Synthesis, in vitro and in vivo antitumor and antiviral activity of novel 1-substituted benzimidazole derivatives

J Enzyme Inhib Med Chem. 2015;30(5):826-45. doi: 10.3109/14756366.2014.979344.

Abstract

A novel series of 5-nitro-1H-benzimidazole derivatives substituted at position 1 by heterocyclic rings was synthesized. Cytotoxicity and antiviral activity of the new compounds were tested. Compound 3 was more active than doxorubicin against A-549, HCT-116 and MCF-7. However, compound 3 showed no activity against human liver carcinoma Hep G-2 cell line. Compounds 9 and 17b (E) showed potency near to doxorubicin against the four cell lines. The acute toxicity of compound 9 on liver cancer induced in rats was determined in vivo. Interestingly, it showed restoration activity of liver function and pathology towards normal as compared to the cancer-bearing rats induced by DENA. Compounds 17a (Z), 17b (E) and 18a (Z) were the most promising compounds for their antiviral activity against rotavirus Wa strain.

Keywords: Antitumor; antiviral; benzimidazoles; cytotoxicity.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Rats
  • Rotavirus / drug effects*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Benzimidazoles
  • benzimidazole