Expanding the chemical space of aryloxy-naphthoquinones as potential anti-Chagasic agents: synthesis and trypanosomicidal activity

In continuation our effort to research the chemical space of aryloxy-naphthoquinones as potential anti-Chagas agents, we synthesized nine derivatives and these compounds were evaluated in vitro against epimastigote trypomastigote forms Mexican strains Trypanosoma cruzi (T. cruzi). Most are highly active (IC50 < 1.0 µM) compared reference drug benznidazole (Bzn). Then on trypomastigotes, which is showing better potency results than Bzn for 3b 3g. addition, cytotoxicity was determined murine macrophage cell line J774. 3i most selective NINOA INC-5 forms, respectively. Further also have good oral bioavailability according theoretical predictions. Finally, able determine optimal substitution patterns using pharmacophoric models. All provided very useful structural information continue designing naphthoquinone T. cruzi.