Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di- N -oxide derivatives against Giardia lamblia , Trichomonas vaginalis , and Entamoeba histolytica. An in vitro and in silico approach

In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di- -oxide derivatives were evaluated against ( ) ( ), and ( ). The potential mechanism of action determination was approached by analysis on and triosephosphate isomerase ( TIM and TIM, respectively), and on thioredoxin reductase ( ). Enzyme inactivation assays were performed on recombinant G TIM and TrxR. Compound T-167 showed the best giardicidal activity (IC = 25.53 nM) and the highest inactivation efficiency against G TIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC = 9.20 nM) and trichomonacidal (IC = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC = 29.13 nM) and amoebicidal (IC = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best TrxR inhibitors with IC of 16 µM, and 18 µM, respectively.