Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bisbenzimidazole amidines

Bioorg Med Chem. 2009 Mar 15;17(6):2544-54. doi: 10.1016/j.bmc.2009.01.071. Epub 2009 Feb 5.

Abstract

Novel bisbenzimidazoles (4-6), characterized by 3,4-ethylenedioxy-extension of thiophene core, revealed pronounced affinity and strong thermal stabilization effect toward ds-DNA. They interact within ds-DNA grooves as dimmers or even oligomers and agglomerate along ds-RNA. Compounds 4-6 have shown moderate to strong antiproliferative effect toward panel of eight carcinoma cell lines. Compound 5 displayed the best inhibitory potential and in equitoxic concentration (IC(50)=1 x 10(-6)M) induced accumulation of cells in G2/M phase after 48 h of incubation. Fluorescence microscopy showed that 5 entered into live HeLa cells within 30 min, but did not accumulate in nuclei even after 2.5h. Compound 5 inhibited the growth of Trypanosome cruzi epimastigotes (IC(50)=4.3 x 10(-6)M).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Cell Line / drug effects
  • Cell Line, Tumor
  • Circular Dichroism
  • DNA / chemistry
  • DNA / metabolism*
  • Drug Screening Assays, Antitumor
  • Ethidium / chemistry
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microscopy, Fluorescence
  • Nucleic Acid Denaturation
  • RNA / chemistry
  • RNA / metabolism*
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Thiophenes / chemistry
  • Thiophenes / metabolism*
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / growth & development

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Thiophenes
  • RNA
  • DNA
  • Ethidium