Synthesis and activity of 2-arylvinyl-4-quinoline-carboxylic acids and their reduced analogues against Trypanosoma cruzi and Leishmania amazonensis.?

A. LUCZYWO; F. J. ROLDÁN PACHECO; G. MUSCIA; F. M. FRANK; S. ASÍS

CABA

Otro; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Protozoología

Chagas disease and leishmaniasis caused by the protozoan parasitesTrypanosoma cruzi and Leishmania spp., respectively, presenta significant burden across the developing world. About 6-7 millionpeople are estimated to be infected with T. cruzi while leishmaniasistakes 30,000 deaths annually worldwide. Existing therapeuticssuffer from severe side effects, toxicity, complex and prolonged dosingregimens and emerging resistance. Therefore, alternative treatmentsare intensely searched in order to achieve better results, withless side effects and higher patient adherence. We have reportedthe synthesis and antiparasitic activity of 2-aryl-4-quinoline-carboxylicacids, some of them were moderately active against Leishmaniaspp., Plasmodium falciparum and T. cruzi. Moreover, 2-substitutedquinolines and especially 2-arylvinyl (or styryl) derivatives isolatedfrom plants or prepared by synthesis, exhibited a wide spectrum ofbiological activities such as leishmanicidal and trypanocidal. Withthe goal to increase the activity we have prepared two series of2-arilvinyl-4-quinolinecarboxylic acids and their corresponding reducedanalogues 2-(2-arylethyl)-4-quinolinecarboxylic acids. Thefirst series was synthesized from the microwave-assisted condensationreaction of 2-methylquinoline-4-carboxylic acid with a varietyof arylaldehydes under acid catalysis to give the 2-styryl derivatives.The second one was obtained after the catalytic hydrogenation ofeach product.At present, all the evaluated 2-styrylquinoline derivatives and theirreduced analogues showed no activity against T. cruzi (epimastigotes)with IC50 values between 16.6 and 157.4 μM and the referencedrug benznidazole exhibited 5.8 μM. However, all the reducedcompounds were active against L. amazoniensis (promastigotes),with IC50 values between 4.3 and 6.1 μM, meanwhile the referencedrug miltefosine was IC50 28.9 μM. These compounds are promisinghits to be assayed in amastigote forms of the parasite.