New benzimidazolequinones as trypanosomicidal agents

Claudia López-Lira, Ricardo A. Tapia, Alejandra Herrera, Michel Lapier, Juan D. Maya, Jorge Soto-Delgado, Allen G. Oliver, A. Graham Lappin, Eugenio Uriarte

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number104823
JournalBioorganic Chemistry
Volume111
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Aryloxyquinones
  • Molecular docking
  • Old Yellow Enzyme
  • Trypanosoma cruzi
  • Trypanothione reductase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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