Avaliação in vitro do potencial anti-leishmania infatum e anti-trypanosoma de compostos sintéticos marinhos

Martins, Ligia Ferreira

A leishmaniose e a doença de Chagas são infecções causadas por protozoários que afetam milhões de pessoas em todo o mundo. São encontradas em regiões tropicais e subtropicais, afetando populações menos favorecidas e causando alta mortalidade e morbidade. Considerando o restrito arsenal terapêutico na leishmaniose e a elevada toxicidade dos fármacos disponíveis para seu tratamento, verifica-se a necessidade urgente da pesquisa de novas terapias. Compostos marinhos apresentam elevado potencial antiparasitários. A complexidade estrutural, juntamente com as atividades biológicas relatadas de compostos guanidínicos os tornam alvo de escolha para os estudos de desenho de fármacos. O presente trabalho teve como objetivo estudar a atividade anti-Leishmania (L.) infantum e anti-Trypanosoma cruzi de compostos guanidínicos sintetizados com base em protótipos marinhos naturais. Dentre os 14 compostos testados contra tripomastigotas de Trypanosoma cruzi, onze mostraram atividade. O composto mais ativo foi o BA-22, apresentando CE50 no valor de 3 µM, já o menos ativo foi o composto BA-1, com valor de 88 µM. Os compostos BA-13, BA-18, BA-22, BA-30, GB-118 e PMH-6 apresentaram valores de CE50 inferior a 10 µM. Os compostos BA-13, BA-18, BA-22, BA-30... (AU)

Leishmaniasis is a parasitic protozoan infection, found in tropical and subtropical regions, affecting the poorest population causing high mortality and morbidity. Considering the small number of drugs in clinical use against Leishmaniasis and their high toxicity and long-duration treatments, the need for new therapeuticals is urgent. In this work we study synthetic guanidine derivative of marine invertebrates, in particular are by the most prolific source of all natural guanidine derivates. The structural complexity of these compounds and their potent biological activities make these compounds a target of choice for studies in organic synthesis. Among 14 guanidines compounds 9 showed activity against promastigotes of Leishmania and 11 against trypomastigotes of Trypanosona cruzi, with IC50 ranging between 6.6 - 109,3 µM and and 3,6 -88,5µM respectively. Intracellular forms of Leishmania (L.)infantum were also evaluated, showing IC50 between 2.3 and 18.8 uM. The compounds displayed moderate to low cytotoxicity against mammalian cells in the range between 42,2 µM to > 150 µM. To investigate particular activity against amastigotes could be related to a possible immunomodulatory activity of the compounds in host cells, we evaluated the production of cytokines by macrophages in the presence of compounds EB-3 and GB-118, which was the most selective compounds. In our studies, EB-3, and GB-118 induced no regulation in macrophages, suggesting that no activation of the mediator by the host. Furthermore, the analysis in flow cytometry demonstrated that EB-3 compounds and GB-118 significantly suppressed the... (AU)