Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives. (August 2018)

• Record Type: Journal Article
• Authors: Mafud, Ana C.; Silva, Marcos P.N.; Nunes, Geandra B.L.; de Oliveira, Milene A.R.; Batista, Larissa F.; Rubio, Thiago I.; Mengarda, Ana C.; Lago, Eloi M.; Xavier, Rogério P.; Gutierrez, Stanley J.C.; Pinto, Pedro L.S.; da Silva Filho, Ademar A.; Mascarenhas, Yvonne P.; de Moraes, Josué
• Is Part Of: Toxicology in vitro. Volume 50(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-08
• Subjects: Riparin derivatives -- Structural analysis -- Theoretical calculations -- ADMET -- Antischistosomal compounds; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.02.012
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 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 ~10 μM). 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. Highlights: Riparin E and F showed antischistosomal activity against Schistosoma mansoni . Riparins E and F caused death of worms at low concentrations with no cytotoxicity. Confocal laser scanning microscopy showed morphological and tegumental alterations. In silico analysis revealed a promising ADMET profile for selected riparins.