In vitro activity 2-styryl-4-quinolincarboxilic acids against Trypanosoma cruzi

A. LUCZYWO; G. C. MUSCIA; S. ASÍS

CABA

Congreso; Drug Discovery of Neglected Diseases International Congress 2018. 4th Meeting of ResNet NPND; 2018

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is potentially fatal. It is estimated that thereare between 6 and 7 million infected people in the world [1]. Existing therapies for this neglected tropical disease havesevere side effects, complex and prolonged dosing regimens, high toxicity, and emerging resistance. Therefore, there isa growing need to find alternative treatments.Our research group has reported that 2-substituted quinolines [2] and especially 2-arylvinyl (or styryl) derivatives isolatedfrom plants [3] or prepared by synthesis, exhibited a broad spectrum of biological activities such as leishmanicide andtrypanocide. In order to increase the antichagasic activity, we have prepared a series of 2-arylvinyl-4-quinolinecarboxylicacids.The 2-styryl-4-quinolinecarboxylic acids were synthesized in two stages. First, 2-methyl-4-quinolinecarboxylic acid1 was obtained by the Pfitzinger reaction, using isatin and acetone as starting reagents in basic medium and byconventional heating. In a second step, the derivatives of 2-styrylquinolines 3 were synthesized by the condensation ofKnoevenagel assisted by microwave irradiation, using the precursor 1 and various arylaldehydes 2 under catalysis withtrifluoroacetic acid (TFA). This homogeneous catalyst made it possible to obtain the acids, stereoselectively, 2-arylvinyl-4-quinolinecarboxylics 3 with trans stereoisomerism