New aryloxy‐quinone derivatives with promising activity on Trypanosoma cruzi. Issue 1 (11th November 2019) - Espinosa‐Bustos, Christian
Abstract: Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy‐quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy‐quinone core were considered for developing new anti‐ T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure–activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy‐quinones with higher potency against the protozoan parasite T. cruzi . Abstract : A new series of aryloxy‐quinones with chemical modifications in three specific moieties on the aryloxy‐quinone core were designed, synthesized, and evaluated in vitro against Trypanosoma cruzi in epimastigote form. Most of the new quinones showed higher potency than nifurtimox, a known pharmaceutical used as a baseline drug. Two of them elicited higher selectivity than nifurtimox against Vero cells. A pharmacophore model was used to map the substitution patterns of the five pharmacophoric features of trypanosomicidal activity