SYNTHESIS AND ACTIVITY OF 2-ARYLVINYL- 4-QUINOLINE-CARBOXYLIC ACIDS AND THEIR REDUCED ANALOGUES AGAINST Trypanosoma cruzi AND Leishmania amazonensis

LUCZYWO A; ROLDAN PACHECO FJ; MUSCIA GC; FRANK FM; ASÍS SE

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAP, SAI, SAIC, SAIB, SAB, SAFE, SAFIS, SAH

Chagas disease and leishmaniasis caused by the protozoan parasites Trypanosoma cruzi and Leishmania spp., respectively, present a significant burden across the developing world. About 6-7 million people are estimated to be infected with T. cruzi while leishmaniasis takes 30,000 deaths annually worldwide. Existing therapeutics suffer from severe side effects, toxicity, complex and prolonged dosing regimens and emerging resistance. Therefore, alternative treatments are intensely searched in order to achieve better results, with less side effects and higher patient adherence. We have reported the synthesis and antiparasitic activity of 2-aryl-4-quinoline-carboxylic acids, some of them were moderately active against Leishmania spp., Plasmodium falciparum and T. cruzi. Moreover, 2-substituted quinolines and especially 2-arylvinyl (or styryl) derivatives isolated from plants or prepared by synthesis, exhibited a wide spectrum ofbiological activities such as leishmanicidal and trypanocidal. With the goal to increase the activity we have prepared two series of 2-arilvinyl-4-quinolinecarboxylic acids and their corresponding reduced analogues 2-(2-arylethyl)-4-quinolinecarboxylic acids. The first series was synthesized from the microwave-assisted condensation reaction of 2-methylquinoline-4-carboxylic acid with a variety of arylaldehydes under acid catalysis to give the 2-styryl derivatives.The second one was obtained after the catalytic hydrogenation of each product.At present, all the evaluated 2-styrylquinoline derivatives and their reduced analogues showed no activity against T. cruzi (epimastigotes) with IC50 values between 16.6 and 157.4 μM and the reference drug benznidazole exhibited 5.8 μM. However, all the reduced compounds were active against L. amazoniensis (promastigotes), with IC50 values between 4.3 and 6.1 μM, meanwhile the reference drug miltefosine was IC50 28.9 μM. These compounds are promisinghits to be assayed in amastigote forms of the parasite.