Abstract
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.
Highlights
• Phthalimido-thiazole derivative as multistage compound
• Prophylactic activity of compound 2i
• 100% on schistosomules mortality
• Reduction of egg number
• Anti-fibrotic activity
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Acknowledgements
The authors would like to thank the animal facilities of the Oswaldo Cruz Foundation (Rio de Janeiro, Brazil) and Aggeu Magalhães Institute, Oswaldo Cruz Foundation, in Recife, Brazil.
Funding
This work was funded by the Oswaldo Cruz Foundation (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Ciência e Tecnologia de Pernambuco (FACEPE). Ana Cristina Lima Leite is receiving a CNPq senior fellowship.
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Carlos André Laranjeira Miranda Filho: investigation, writing—original draft.
Miria de Oliveira Barbosa: investigation
Arsênio Rodrigues Oliveira: compound synthesis
Aline Ferreira Pinto: review and editing
Daniel Lopes Araújo: review and editing
Jéssica Paula Lucena: investigation
Roni Evêncio de Araújo investigation
Sheilla Andrade de Oliveira: supervision, resources, conceptualization
Ana Cristina Lima Leite: supervision, resources. conceptualization, writing—review and editing
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Laranjeira Miranda Filho, C.A., de Oliveira Barbosa, M., Rodrigues Oliveira, A. et al. The prophylactic and anti-fibrotic activity of phthalimido-thiazole derivatives in schistosomiasis mansoni. Parasitol Res 121, 2111–2120 (2022). https://doi.org/10.1007/s00436-022-07533-4
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DOI: https://doi.org/10.1007/s00436-022-07533-4