Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di--oxide derivatives against , , and An and 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 GTIM and TrxR. Compound T-167 showed the best giardicidal activity (IC = 25.53 nM) and the highest inactivation efficiency against GTIM 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.