Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

• DOI: 10.1016/j.ijpddr.2016.07.001
• Publication Date: 2016-07-16T19:07:53Z
• Authors: Guilherme Curty L...; Júlio Cesar Borges; Claudia Magalhães...; Humberto Pinheiro...; Aline Araujo Zuma; Samara Braga do N...; Maria Cristina Ma...; Alice Maria Rolim...; Mirian Claudia de...; Saulo Cabral Bour...
• Keywords: Hemin; Chagas Disease; Amastigote; Benznidazole; Mechanism of Action; Trypanocidal agent; IC50

Chagas disease is a neglected tropical caused by the flagellated protozoan Trypanosoma cruzi. The current drugs used to treat this have limited efficacy and produce severe side effects. Quinolines, nitrogen heterocycle compounds that form complexes with heme, broad spectrum of antiprotozoal activity are promising class new for chemotherapy. In study, we evaluated series 4-arylaminoquinoline-3-carbonitrile derivatives against all forms cruzi in vitro. Compound 1g showed epimastigote when combined hemin (IC50<1 μM), better performance than benznidazole, reference drug. This compound also inhibited viability trypomastigotes intracellular amastigotes. potency combination heme was enhanced epimastigotes trypomastigotes, suggesting similar mechanism action occurs Plasmodium spp. addition culture medium increased trypanocidal analog without changing cytotoxicity host cell, reaching an IC50 11.7 μM trypomastigotes. demonstrated interaction solution prevention peroxidation. treatment induced alterations mitochondrion-kinetoplast complex also, accumulation electron-dense deposits amastigotes as visualized transmission electron microscopy. 4-aminoquinolines elucidation involving field research, given parasite's lack biosynthetic pathway importance cofactor parasite survival growth. results study can improve guide rational drug development strategies.