Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum

Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds...

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Published in:Tropical medicine and infectious disease 2023-02, Vol.8 (3), p.141
Main Authors: Almeida, Fernanda Silva, Moreira, Vitor Partite, Silva, Edson Dos Santos, Cardoso, Leonardo Lima, de Sousa Palmeira, Pedro Henrique, Cavalcante-Silva, Luiz Henrique Agra, Araújo, Demétrius A M de, Amaral, Ian P G do, González, Eduardo René Pérez, Keesen, Tatjana S L
Format: Article
Language:English
Subjects:
anti-leishmanial activity
Antibiotics
Apoptosis
Blood
Cell death
Cytotoxicity
Drugs
guanidine compounds
Leishmaniasis
nitrite production
Parasites
Parasitic diseases
Sodium
Tropical diseases
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Summary:Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds have shown antimicrobial activity, we analyzed the cytotoxic effects of several guanidine-bearing compounds on in their promastigote and amastigote forms in vitro, their cytotoxicity in human cells, and their impact on reactive nitrogen species production. LQOFG-2, LQOFG-6, and LQOFG-7 had IC values of 12.7, 24.4, and 23.6 µM, respectively, in promastigotes. These compounds exhibited cytotoxicity in axenic amastigotes at 26.1, 21.1, and 18.6 µM, respectively. The compounds showed no apparent cytotoxicity in cells from healthy donors. To identify mechanisms of action, we evaluated cell death processes by annexin V and propidium iodide staining and nitrite production. Guanidine-containing compounds caused a significant percentage of death by apoptosis in amastigotes. Independent of infection, LQOFG-7 increased nitrite production in peripheral blood mononuclear cells, which suggests a potential mechanism of action for this compound. Therefore, these data suggest that guanidine derivatives are potential anti-microbial molecules, and further research is needed to fully understand their mechanism of action, especially in anti-leishmanial studies.
ISSN:2414-6366
2414-6366
DOI:10.3390/tropicalmed8030141