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Phthalimido-thiazole as privileged scaffold: activity against immature and adult worms of Schistosoma mansoni

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Abstract

Phthalimide, 1,3-thiazole, and thiazolidinone cores are considered privileged scaffolds and represent an attractive starting point to design new bioactive compounds for neglected tropical disease (NTD). Schistosomiasis is a NTD, caused by Schistosoma worms which praziquantel (PZQ) is the only drug used to treat humans, but the decrease in the effect after treatment has been reported. Recently, some phthalimide-thiazole derivatives exhibited in vitro antischistosomal activity against adult worms with significant ultrastructural changes and a lower cytotoxic effect on splenocytes. This new biological phthalimido-thiazole profile has motivated us to evaluate a new generation of such molecules in immature and adult worms. Thus, a phthalimido-thiazolidinone derivative, (3c), and three phthalimido-thiazoles (6c, 7a, and 7h) were evaluated concerning their in vitro activity on schistosomulae and adult worms. The results showed that these compounds brought a significant reduction on the mortality, inhibited oviposition, and then induced mortality in immature and adult worms alike. According to scanning electron microscopy, the tegument was the principal target for 7a and 7h and revealed gradual damage to the tegument surface, inducing destruction and decomposition of the tegument in the same areas and exposition of subtegumental tissue and of muscle tissue. Furthermore, they caused less toxicity in splenocytes than PZQ. Compounds 7a and 7h revealed to possess promising activity against larval forms. According to the present study, the privileged structure phthalimido-thiazoles act as a molecular framework that has antischistosomal activity and most form the basis to the next pre-clinical tests.

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Acknowledgements

The authors thank the animal facility of the Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, and Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, in Recife, Brazil. The present study was supported by Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo a Ciência e Tecnologia de Pernambuco (FACEPE). Miria de Oliveira Barbosa and Paulo André Teixeira de Moraes Gomes receive a FACEPE scholarship. Ana Cristina Lima Leite is a CNPq senior fellow.

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Authors and Affiliations

  1. Department of Immunology, Laboratory of Immunopathology and Molecular Biology, IAM/FIOCRUZ, Recife, PE, CEP: 50670-420, Brazil

    Sheilla Andrade de Oliveira, Miria de Oliveira Barbosa & Edna de Farias Santiago

  2. Department of Pharmaceutical Sciences, Federal University of Pernambuco, S/N—Campus da UFPE, Recife, PE, CEP: 50740-520, Brazil

    Miria de Oliveira Barbosa, Carlos André Laranjeira Miranda Filho, Arsênio Rodrigues Oliveira, Fabiano Amaro de Sousa, Gevanio Bezerra de Oliveira Filho, Paulo André Teixeira de Moraes Gomes, Juliana Maria da Conceição & Ana Cristina Lima Leite

  3. Keizo Asami Immunopathology Laboratory (LIKA), Av. Professor Moraes Rego, S/N—Campus da UFPE, Recife, PE, CEP: 50670-420, Brazil

    Fábio André Brayner & Luiz Carlos Alves

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  1. Sheilla Andrade de Oliveira
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  2. Miria de Oliveira Barbosa
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  3. Carlos André Laranjeira Miranda Filho
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  12. Ana Cristina Lima Leite
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Correspondence to Ana Cristina Lima Leite.

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de Oliveira, S.A., de Oliveira Barbosa, M., Filho, C.A.L.M. et al. Phthalimido-thiazole as privileged scaffold: activity against immature and adult worms of Schistosoma mansoni. Parasitol Res 117, 2105–2115 (2018). https://doi.org/10.1007/s00436-018-5897-4

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