Dados do Trabalho

Título

In vitro evaluation of thiosemicarbazone compounds against Leishmania infantum as potential therapeutic agents

Introdução

Leishmaniasis which is caused by various Leishmania species, remains a persistent public health concern. Current treatments involve pentavalent antimonials, amphotericin B, pentamidine, and methylphosine, but their side effects and cytotoxicity have prompted the exploration of alternative options. Synthetic compounds such as thiosemicarbazone derivatives, which offer versatility, cost-effectiveness, and high chemoselectivity due to their modified chemical structures, have emerged as potential therapeutics.

Objetivo (s)

The objective of this work is to perform in vitro studies in the evaluation of the leishmanicidal activity against Leishmania infantum as an innovative alternative in the search for new candidate molecules for new therapeutic agents.

Material e Métodos

This study aims to assess the leishmanicidal activity of eight thiosemicarbazone compounds (JF-257, JF-258, JF-259, JF-260, JF-262, JF-264, JF-265, JF-266) against L. infantum promastigotes in vitro. The evaluation includes determining the compounds' IC50, Selectivity Index (SI), and cytotoxicity (CC50) in j774 macrophages, HEPG2, and Vero cells. Additionally, ultrastructural analysis of L. infantum promastigotes was conducted using transmission and scanning electron microscopy.

Resultados e Conclusão

Preliminary results demonstrated that all tested compounds exhibited leishmanicidal activity, inhibiting the growth of L. infantum promastigotes. The most effective compounds were JF-264 (IC50 = 4.03 μg/mL) and JF-260 (IC50 = 5.16 μg/mL). CC50 values for J774 macrophages ranged from 12.59 to 44.66 μg/mL, with JF-266 displaying the highest SI. CC50 values for Vero cells ranged from 9.888 to 19.0 μg/mL, and JF-260 exhibited the highest SI. CC50 values for HEPG2 cells ranged from 7.09 to 11.08 μg/mL, with JF-260 again showing the highest SI. Ultrastructural analysis revealed morphological alterations in L. infantum promastigotes treated with JF-260 and JF-266, including rounded and swollen cells with reduced flagella. Transmission electron microscopy further displayed changes such as parasite shrinkage, cytoplasmic vacuolation, electron-dense inclusions, mitochondrial swelling, nuclear disfigurement, and cell rarefaction. Thiosemicarbazone compounds have shown promising efficacy against Leishmania species, selectively targeting the parasite. Further research is needed to understand their mechanisms of action and explore their potential as therapeutic agents.

Palavras-chave

Thiosemicarbazones; Leishmania infantum; anti-leishmania; in vitro

Agradecimentos

FACEPE (IBPG-0221-2.13/20)