Thiazolidine derivatives: In vitro toxicity assessment against promastigote and amastigote forms of Leishmania infantum and ultrastructural study.

Autor: Gouveia ALA; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Santos FAB; Aggeu Magalhães Institut. Oswaldo Cruz Foundation (IAM-FIOCRUZ), 50670-420, Recife, PE, Brazil., Alves LC; Aggeu Magalhães Institut. Oswaldo Cruz Foundation (IAM-FIOCRUZ), 50670-420, Recife, PE, Brazil., Cruz-Filho IJ; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Silva PR; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Jacob ITT; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Soares JCS; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Santos DKDN; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil., Souza TRCL; Rural University of Pernambuco, Academic Unit of Belo Jardim, 55156-580, Belo Jardim, PE, Brazil., Oliveira JF; University for the International Integration of Afro-Brazilian Lusophony (UNILAB), 62790-970, Redenção, CE, Brazil., Lima MDCA; Federal University of Pernambuco, Department of Antibiotics, Center for Biosciences, 50.670-420, Recife, PE, Brazil. Electronic address: maria.calima@ufpe.br.
Jazyk: angličtina
Zdroj: Experimental parasitology [Exp Parasitol] 2022 May-Jun; Vol. 236-237, pp. 108253. Date of Electronic Publication: 2022 Apr 04.
DOI: 10.1016/j.exppara.2022.108253
Abstrakt: Neglected diseases, such as Leishmaniasis, constitute a group of communicable diseases that occur mainly in tropical countries. Considered a public health problem with limited treatment. Therefore, there is a need for new therapies. In this sense, our proposal was to evaluate in vitro two series of thiazolidine compounds (7a-7e and 8a-8e) against Leishmania infantum. We performed in vitro evaluations through macrophage cytotoxicity assays (J774) and nitric oxide production, activity against promastigotes and amastigotes, as well as ultrastructural analyzes in promastigotes. In the evaluation of cytotoxicity, the thiazolidine compounds presented CC 50 values between 8.52 and 126.83 μM. Regarding the evaluation against the promastigote forms, the IC 50 values ranged between 0.42 and 142.43 μM. Compound 7a was the most promising, as it had the lowest IC 50 . The parasites treated with compound 7a showed several changes, such as cell body shrinkage, shortening and loss of the flagellum, intense mitochondrial edema and cytoplasmic vacuolization, leading the parasite to cell inviability. In assays against the amastigote forms, the compound showed a low IC 50 (0.65 μM). These results indicate that compound 7a was efficient for both evolutionary forms of the parasite. In silico studies suggest that the compound has good oral bioavailability. These results show that compound 7a is a potential drug candidate for the treatment of Leishmaniasis.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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