Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI

Bioorg Med Chem Lett. 2016 Dec 15;26(24):5907-5910. doi: 10.1016/j.bmcl.2016.11.006. Epub 2016 Nov 3.

Abstract

A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.

Keywords: Antitrypanosomal activity; Benzimidazole diamidines; DAPI; DNA minor groove binders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / chemical synthesis
  • Amidines / chemistry
  • Amidines / pharmacology*
  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Binding Sites / drug effects
  • Cells, Cultured
  • DNA / drug effects*
  • Dose-Response Relationship, Drug
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Myoblasts / drug effects
  • Parasitic Sensitivity Tests
  • Rats
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei rhodesiense / drug effects*

Substances

  • Amidines
  • Benzimidazoles
  • Indoles
  • Trypanocidal Agents
  • DAPI
  • DNA
  • benzimidazole