Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. L. infantum is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against L. infantum is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound 32 (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC50 = 33.71 μM) with the highest selectivity index (SI > 42.46), followed by compound 15 (piperonyl cinnamate) with an IC50 = 42.80 μM and SI > 32.86. Compound 32 was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in L. infantum was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against Leishmania species.

Dedico este trabalho de conclusão de curso aos meus pais Maria Valdena e José Alves. E aos meus irmãos Jefersson e Ricardo. Pelo apoio e incentivo que sempre me deram. iii AGRADECIMENTOS Agradeço a Deus pelo dom da vida, por me permitir acordar todos os dias e desfrutar das maravilhas criadas por Ele sentindo sua presença e amor em cada momento, em cada gesto. Agradeço pela minha família e pelos meus amigos, a família que Ele me permitiu escolher. Agradeço a minha mãe e ao meu pai pelo amor, carinho e incentivo. Se não fosse o esforço deles em buscar um ensino de qualidade para minha formação eu não teria chegado onde estou hoje. Agradeço aos meus irmãos pelo companheirismo e ajuda, sempre pude contar com eles.Agradeço aos meus amigos de semestre que tornaram essa jornada tão divertida quando ela poderia ser: