Dados do Trabalho

Name: 58º Congresso da Sociedade Brasileira de Medicina Tropical
Start: 2023-09-10
End: 2023-09-13
Location: Centro de Convenções de Salvador

Título

ANTILEISHMANIAL ACTIVITY OF ANTIHISTAMINE DRUGS: AZELASTINE AND CLEMASTINE IN Leishmania infantum

Introdução

The search for new drugs for Leishmaniasis is becoming increasingly necessary given the infeasibility of current therapeutic regimens. The few drugs available have variable efficacy, high toxicity, and an inconvenient therapeutic scheme. The drug repositioning strategy has been highlighted for its interesting results in research. Drugs from the antihistamine class are one of the most used, especially for allergy treatment. Previous studies have already reported their in vitro activity against species of Leishmania, indicating that they can cause alterations and death of the parasite.

Objetivo (s)

Determine the antileishmanial activity of the antihistamine drugs azelastine (AZL) and clemastine (CMT) against Leishmania infantum.

Material e Métodos

Antileishmanial activity against promastigotes and amastigotes of L. infantum and cytotoxic in mammalian cells (NCTC L-929) were determined, using phenotypic assays. Promastigotes and NCTC were incubated with drugs for different periods, thus the cell viability was verified by colorimetric assay using the MTT reagent. Amastigotes were isolated and cultured in intraperitoneal macrophages, and incubated with drugs, after the treatment they were stained with Giemsa and observed in an optical microscope, to determine the infection index. The Selectivity Index (SI) of these drugs was also calculated between cytotoxicity and activity in promastigotes.

Resultados e Conclusão

AZL and CMT showed more efficacy against promastigote at 50% Effective Concentration of 2.10 ± 0.03 µM and 0.96 ± 0.07 µM, respectively, compared to the standard drug miltefosine (MTF) (14.69 ± 0.24 µM). In amastigote forms, AZL and CMT were able to reduce the rate of macrophage infection by 100% in a concentration of 25 µM, when compared with MTF at the same concentration, reducing only 50% of the infection. AZL and CMT showed the 50% Cytotoxic Concentration in mammalian cells of 32.62 ± 1.97 and 18.25 ± 0.10 µM, respectively. The SI for AZL was 15.8 and for CLM was 19. This study reported the antiparasitic activity in L. infantum of two antihistamines, to select new compounds that may contribute to the research of drugs for Visceral Leishmaniasis.