The prophylactic and anti-fibrotic activity of phthalimido-thiazole derivatives in schistosomiasis mansoni.

Autor: Laranjeira Miranda Filho CA; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, Aggeu Magalhães Institute, FIOCRUZ, Recife, PE, Brazil., de Oliveira Barbosa M; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, Aggeu Magalhães Institute, FIOCRUZ, Recife, PE, Brazil.; Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), S/N, Recife, PE, CEP 50740-525, Brazil., Rodrigues Oliveira A; Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), S/N, Recife, PE, CEP 50740-525, Brazil., Ferreira Pinto A; Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), S/N, Recife, PE, CEP 50740-525, Brazil., Araújo DL; Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), S/N, Recife, PE, CEP 50740-525, Brazil., Lucena JP; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, Aggeu Magalhães Institute, FIOCRUZ, Recife, PE, Brazil., de Araújo RE; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, Aggeu Magalhães Institute, FIOCRUZ, Recife, PE, Brazil., de Oliveira SA; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, Aggeu Magalhães Institute, FIOCRUZ, Recife, PE, Brazil., Lima Leite AC; Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), S/N, Recife, PE, CEP 50740-525, Brazil. ana.lleite@ufpe.br.
Jazyk: angličtina
Zdroj: Parasitology research [Parasitol Res] 2022 Jul; Vol. 121 (7), pp. 2111-2120. Date of Electronic Publication: 2022 May 23.
DOI: 10.1007/s00436-022-07533-4
Abstrakt: Schistosomiasis mansoni is considered a serious public health problem. As praziquantel is the only drug recommended by the World Health Organization for the treatment and control of schistosomiasis, the development of new drugs is of great significance. In this work, we present the antischistosomal activity of a small set of phthalimido-thiazole derivatives against Schistosoma mansoni. The effects of those derivatives on the viability of larvae juveniles and adult parasites, production and development of eggs, mortality of schistosomules in vitro by counting worms, and stages of eggs of infected animals in acute and chronic phases were evaluated, resulting in the identification of new multistage antischistosomal compounds. Additionally, a study of liver fibrogenesis was released. The phthalimido-thiazole derivatives, compounds 2b-d, 2h-j, had shown activity on schistosomules, achieving 100% mortality even at 5 mg/mL, in the first 24 h. In the chronic phase of schistosomiasis infection, compound 2i promoted a reduction in the number of immature eggs, an increase in the number of non-viable parasite eggs, a reduction in the average number of eggs in the liver and intestine, decrease in the levels of hydroxyproline in the liver, and a reduction in the areas of hepatic fibrosis. This compound also promoted an increase of IL-10 and a reduction in the level of TNF-α in the liver. Accordingly, the phthalimide-thiazole scaffold is a new starting point for the development of multistage compounds that affect S. mansoni viability, egg formation, and production.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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