Title
Evidence of Guanidines Potential against Leishmania (Viannia) braziliensis: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects
Author
Luana Ribeiro dos Anjos
Fine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Brazil
Author
Vanessa Maria Rodrigues de Souza
Infectious Disease Laboratory—LADIC, Federal University of Parnaíba Delta—UFDPar, Campus Ministro Reis Velloso, Brazil
Author
Yasmim Alves Aires Machado
Infectious Disease Laboratory—LADIC, Federal University of Parnaíba Delta—UFDPar, Campus Ministro Reis Velloso, Brazil
... show all
Abstract
Leishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molecules that offer greater effectiveness and safety. This study sought to explore the impact of seven synthetic guanidine derivatives (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 and LQOF-G36) onthe parasite Leishmania (Viannia) braziliensis and in vitro macrophage infection by this parasite, as well as cytotoxic approaches in vitro models of mammalian host cells and tissues. The synthesized compounds showed purity ≥ 99.65% and effectively inhibited parasite growth. LQOF-G1 proved the most potent, yielding the best half-maximal inhibitory concentration (IC50) values against promastigotes (4.62 μmol/L), axenic amastigotes (4.27 μmol/L), and intracellular amastigotes (3.65 μmol/L). Notably, the antileishmanial activity of LQOF-G1, LQOF-G2, and LQOF-G6 was related to immunomodulatory effects, evidenced by alterations in TNF-α, IL-12, IL-10, nitric oxide (NO), and reactive oxygen species (ROS) levels in the supernatant of culture macrophages infected with L. (V.) braziliensis and coincubated with these compounds. LQOF-G2 and LQOF-G36 compounds exhibited vasodilator and spasmolytic effects at higher concentrations (≥100 μmol/L). Generally, LQOF-G1, LQOF-G2, and LQOF-G32 compounds were found to be nontoxic to assessed organs and cells. No toxic effects were observed in human cell lines, such as HEK-293, CaCo-2 and A549, at concentrations ≥ 500 μmol/L. Collectively, data have shown unequivocal evidence of the effectiveness of these compounds against L. (V.) braziliensis parasite, one of the causative agents of Tegumentary Leishmaniasis and Mucocutaneous Leishmaniasis in America.
Keywords
guanidine derivativesLeishmania (Viannia) braziliensisimmunomodulationorgan and cell toxicity
Object type
Language
English [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:2072413
Appeared in
Title
Biomolecules
Volume
14
Issue
1
ISSN
2218-273X
Issued
2023
From page
26
Publisher
MDPI AG
Date issued
2023
Access rights
Rights statement
© 2023 by the authors.

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