Banca de DEFESA: ALICE DOS SANTOS ROSA
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : ALICE DOS SANTOS ROSA
DATA : 30/03/2020
HORA: 10:00
LOCAL: Remotamente através da plataforma hangout
TÍTULO:
EVALUATION OF THE LEISHMANICIDE EFFECT OF 1, 3, 4 THIADIAZOLIUM MESOIONIC DERIVATIVES ON Leishmania amazonensis IN VITRO.
PALAVRAS-CHAVES:
Leishmaniasis, Leishmania (Leishmania) amazonensis, 1,3,4 -thiadiazolium derivatives, mesoionic salts, treatment
PÁGINAS: 79
GRANDE ÁREA: Ciências Biológicas
ÁREA: Parasitologia
SUBÁREA: Protozoologia de Parasitos
ESPECIALIDADE: Protozoologia Parasitária Animal
RESUMO:
Leishmaniasis is a group of neglected diseases caused by protozoa of the genus Leishmania, which affect millions of people annually in the world. Besides human beings, the disease also affects dogs, which are the main domestic reservoir of the disease. In humans, Leishmaniasis presents a broad clinical spectrum, and in dogs causes viscero-cutaneous manifestations. Drugs used in treatment have a high toxicity, presents several side effects, and have high production costs. In addition, in endemic countries, resistant strains have been reported. Therefore, the search of new bioactive molecules is necessary. Mesoionic salts are a subclass of the betaine group, widely studied since the 1950s, and exhibit extensive biological activity. Our work aims to analyze the cytotoxic effects of mesoionic compounds 4-phenyl-5-(X-phenyl)-1,3,4-thiadiazolium-2-phenylamine (X= 4 Cl; 3.4 diCl and 3.4 diF) on Leishmania amazonensis in vitro. To evaluate the anti-promastigote effect, L. amazonensis promastigotes were incubated in different concentrations of mesoionic salts during 72 hours. Our results show that the mesoionic salts MI-3.4 diCl, MI-4Cl and MI-3.4 diF were toxic, with IC50 values of 14.3, 40.1 and 61.8 μM, respectively. The anti-amastigote effect was evaluated in infected macrophages, and results demonstrate that chlorine compounds have a toxic effect against amastigotes with IC50 of 33 μM (MI-4Cl) and 43 μM (MI-3.4diCl). None of the mesoionic compounds tested present host cell toxicity up to the tested concentration of 200 μM. Nitric oxide (NO) production in macrophages stimulated or not with LPS in the presence of the salts showed that only the MI-3.4 diCl compound reduced NO levels by two times. Lipid profile analysis of treated-promastigotes showed no significant alteration of neutral lipids. Mitochondrial membrane potential evaluation showed that MI-4Cl compound was the only one able to reduce mitochondrial membrane potential by 50%. Therefore, the results suggest that the mesoionic salts MI-4Cl and MI-3,4diCl have a potential anti-leishmania effect.
MEMBROS DA BANCA:
Interna - 1222756 - DEBORA DECOTE RICARDO DE LIMA
Interna - 1545840 - LUCIA HELENA PINTO DA SILVA
Interna - 1792175 - PATRICIA FAMPA NEGREIROS LIMA
Externo à Instituição - EDUARDO CAIO TORRES DOS SANTOS - FIOCRUZ
Externa à Instituição - JULIANY COLA FERNANDES RODRIGUES - UFRJ