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Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives

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Autor(es):
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Mafud, Ana C. [1] ; Silva, Marcos P. N. [2] ; Nunes, Geandra B. L. [3] ; de Oliveira, Milene A. R. [1] ; Batista, Larissa F. [1] ; Rubio, Thiago I. [1] ; Mengarda, Ana C. [2] ; Lago, Eloi M. [2] ; Xavier, Rogerio P. [2] ; Gutierrez, Stanley J. C. [4] ; Pinto, Pedro L. S. [5] ; da Silva Filho, Ademar A. [6] ; Mascarenhas, Yvonne P. [1] ; de Moraes, Josue [2]
Número total de Autores: 14
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Paulo - Brazil
[2] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, Sao Paulo - Brazil
[3] Univ Fed Piaui, Lab Pesquisa Neuroquim Expt, Teresina, Piaui - Brazil
[4] Univ Fed Piaui, Lab Quim Prod Nat & Sintet Bioact, Teresina, Piaui - Brazil
[5] Adolfo Lutz Inst, Nucleo Enteroparasitas, Sao Paulo - Brazil
[6] Univ Fed Juiz de Fora, Dept Ciencias Farmaceut, Fac Farm, Juiz De Fora, MG - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: TOXICOLOGY IN VITRO; v. 50, p. 1-10, AUG 2018.
Citações Web of Science: 6
Resumo

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values similar to 10 mu M). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties. (AU)

Processo FAPESP: 14/02282-6 - Estudo da relação estrutura-atividade de alcalóides derivados da Pilocarpus microphyllus (Rutaceae) com ação contra Schistosoma mansoni
Beneficiário:Ana Carolina Mafud
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
Beneficiário:Josué de Moraes
Linha de fomento: Auxílio à Pesquisa - Regular