Study of in vitro biological activity of thiazoles on Leishmania (Leishmania) infantum.

Abstract Objectives In the prospection of possible agents against neglected diseases, thiazole compounds are presented as promising candidates and are known to have activity against trypanosomatid parasites. Thus, this work aimed to evaluate the effects of thiazole compounds on Leishmania infantum, etiological agent of visceral leishmaniasis. Methods Thiazole compounds, being 5 thiazoacetylpyridines (TAPs-01; 04; 05; 06; 09) and 5 thiazopyridines (TPs-01; 04; 05; 06; 09) were tested regarding its leishmanicidal activity on both promastigote and amastigote forms of L. infantum. Its cytotoxicity was tested using peritoneal macrophages of BALB/c mice. Ultrastructural analyzes were performed to identify possible intracellular targets of the most effective compound on promastigote forms. In order to observe routes that can clarify the possible mechanism of action of the compounds on the intracellular amastigote forms, the Nitrite dosage was performed. Results All compounds inhibited the growth of promastigote and presented low cytotoxicity, being more selective to the parasite than to mammalian cells. All compounds tested were able to decrease macrophage infection. There was a significant decrease in the survival rate of the amastigote when compared to the untreated cells, with TAP-04 presenting the best index. TAP-04 compound induced ultrastructural changes that are relted to cell death by apoptosis. None of the macrophage groups infected with L. infantum and subsequently treated showed increased nitrite release. Conclusions The low toxicity to mammalian cells and the leishmanicidal activity observed demonstrate that the synthesis of drugs based in thiosemicarbazone nucleus, thiazole and pyridine derivatives are promising to the treatment of VL.