Banca de DEFESA: ALICE DOS SANTOS ROSA
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : ALICE DOS SANTOS ROSA
DATA : 26/03/2020
HORA: 09:00
LOCAL: ICBS - Salão Vermelho
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 are a group of neglected diseases, caused by the protozoan of the genus Leishmania, which affects millions of people annually worldwide and also affects dogs, the main domestic reservoir of the disease. This disease has a broad clinical spectrum in man and in the dog it causes a visceral-cutaneous disease. The drugs used in treatment have a high toxicity, which cause severe side effects, and have high production cost. In addition, in endemic countries, cases of resistant strains have been reported. All of these, make the search for new bioactive molecules necessary. Mesoionic salts are a subclass of the betaine group characterized by the presence of an aromatic ring formed by five members, which has a partial positive charge counterbalanced by a negatively charged exocyclic hetero atom, which have anti-tumor, anti-oxidant and microbicide activities. The aim of our work is 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 with different concentrations of mesoionic salts for 72 hours. Our results demonstrate that the mesoionic salts MI-3,4 diCl, MI-4Cl and MI-3,4 diF were toxic, with IC 50 values of 14.3, 40.1 and 61.8 µM, respectively. The anti-amastigote effect was evaluated in murine infected-macrophages and our results demonstrate that the chlorinated compounds have a toxic effect against amastigotes with an IC50 of 33 µM (MI-4Cl) and 43 µM (MI-3,4diCl). None of the mesoionic compounds tested showed toxicity to the host cell up to 200 µM. Nitric oxide (NO) production in macrophages stimulated or not with LPS in the presence of salts demonstrated that only MI-3,4 diCl compound reduced NO levels by up to 2x. The analysis of the lipid profile of treated-promastigotes did not show changes in neutral lipids profile. The evaluation of the mitochondrial potential membrane showed that the compound MI-4Cl was able to reduce the mitochondrial potential membrane by 50%. Based on these results, our data suggest that the MI-4Cl and MI-3,4diCl mesoionic salts have a potential anti-leishmania effect.
MEMBROS DA BANCA:
Presidente - 1545840 - LUCIA HELENA PINTO DA SILVA
Interna - 1222756 - DEBORA DECOTE RICARDO DE LIMA
Interna - 1792175 - PATRICIA FAMPA NEGREIROS LIMA
Externo à Instituição - EDUARDO CAIO TORRES DOS SANTOS - FIOCRUZ
Externa à Instituição - JULIANY COLA FERNANDES RODRIGUES - UFRJ