New benzimidazolequinones as trypanosomicidal agents

Bioorg Chem. 2021 Jun:111:104823. doi: 10.1016/j.bioorg.2021.104823. Epub 2021 Mar 12.

Abstract

Herein, the design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives as potential anti-Trypanosoma cruzi agents are described. The compounds were evaluated in vitro against the epimastigotes and trypomastigote forms of Trypanosoma cruzi. The replacing of a benzene moiety in the naphthoquinone system by an imidazole enhanced the trypanosomicidal activity against Trypanosoma cruzi. Three of the tested compounds (11a-c) showed potent trypanosomicidal activity and compound 11a, with IC50 of 0.65 μM on the trypomastigote form of T. cruzi, proved to be 15 times more active than nifurtimox. Additionally, molecular docking studies indicate that the quinone derivatives 11a-c could have a multitarget profile interacting preferentially with trypanothione reductase and Old Yellow Enzyme.

Keywords: Aryloxyquinones; Molecular docking; Old Yellow Enzyme; Trypanosoma cruzi; Trypanothione reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Quinones / chemical synthesis
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*

Substances

  • Benzimidazoles
  • Quinones
  • Trypanocidal Agents
  • benzimidazole