New benzimidazolequinones as trypanosomicidal agents

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 mu M 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.

Automated summary

The design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives demonstrate potent anti-Trypanosoma cruzi activity. Compound 11a shows significantly higher activity compared to nifurtimox. Molecular docking studies suggest that these compounds could have a multitarget profile.