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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 14
[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
Total Affiliations: 6
Document type: Journal article
Source: TOXICOLOGY IN VITRO; v. 50, p. 1-10, AUG 2018.
Web of Science Citations: 6

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)

FAPESP's process: 14/02282-6 - Structure-activity relationship studies about of Pilocarpus microphyllus (Rutaceae) alkaloid derivatives against Schistosoma mansoni
Grantee:Ana Carolina Mafud
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/22488-3 - Drug repositioning for neglected diseases: identification of novel anthelmintic agents
Grantee:Josué de Moraes
Support type: Regular Research Grants