Síntese e avaliação anti-Leishmania de novos derivados híbridos tiofênicos-acridínicos

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Serafim, Vanessa de Lima
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraíba
Brasil
Biologia Celular e Molecular
Programa de Pós-Graduação em Biologia Celular e Molecular
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/9460
Resumo: Leishmaniasis is a group of diseases caused by protozoa of the genus Leishmania, transmitted by sand flies insects. As recommended treatments are toxic and not very satisfactory, it is necessary to find new drugs more effective against the parasite and that have low toxicity to the host. In this context, this study aimed to synthesize, structurally elucidate and evaluate the anti-Leishmania potential novel hybrids thiophenics-acridines front of promastigotes of Leishmania (L.) amazonensis. In this study, we evaluated 23 compounds, of which 14 were derived hybrids. The synthesis of compounds had a yield from 47.7% (ACT06) to 88% (ACT05) to ACT series, and ACS series from 44.8% (ACS05) to 94.9% (ACS02). All compounds of ACS series showed antipromastigote activity (IC50 values from 3.9 to 30.9 μg/mL). Differently, hybrids of ACT series no showed antiparasitic activity. None of the derivatives showed cytotoxicity to erythrocytes of human origin, as compared to reference drug. The compounds with improved activity, ACS01 and ACS02 (IC50 3.9 and 4.6 μg/mL; SI 205.1 and 173.9 respectively) were selected to proceed with the investigation. ACS01 and ACS02 were effective against strains resistant trivalent antimony in the same way as in sensitive strains. Furthermore, the activity of ACS01is not associated with parasite DNA fragmentation, but ACS01 and ACS02 showed a binding constant of 104 M-1, demonstrating their DNA intercalation capacity. Thus, these results suggest that the derivatives of the ACS series are possible drug candidates for the therapy of leishmaniasis.