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New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment
Paul Coulerie, Alexandre Maciuk, Cécilia Eydoux, Edouard Hnawia, Nicolas Lebouvier, Bruno Figadère, Jean-Claude Guillemot and Mohammed Nour
Laboratoire Insulaire du Vivant et de l’Environnement, Université de la Nouvelle-Calédonie, BP R4, 98851 Nouméa Cedex, Nouvelle-Calédonie
Laboratoire BioCIS, UMR CNRS 8076 Université Paris-Sud XI, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France
Laboratoire AFMB, UMR 6098, Université Aix-Marseille, Campus de Luminy, 13288 Marseille cedex 09, France
Abstract: Since a few decades the dengue virus became a major public health concern and no treatment is available yet. In order to propose potential antidengue compounds for chemotherapy we focused on DENV RNA polymerase (DENV-NS5 RdRp) which is specific and essential for the virus replication. Carpolepis laurifolia belongs to the Myrtaceae and is used as febrifuge in traditional kanak medicine. Leaf extract of this plant has been identified as a hit against the DENV-NS5 RdRp. Here we present a bioguided fractionation of the leaf extract of C. laurifolia which is also the first phytochemical evaluation of this plant. Five flavonoids, namely quercetin (1), 6-methyl-7-methoxyapigenin (2), avicularin (3), quercitrin (4) and hyperoside (5), together with betulinic acid (6), were isolated from the leaf extract of C. laurifolia. All isolated compounds were tested individually against the DENV-NS5 RdRp and compared with four other commercial flavonoids: isoquercitrin (7), spiraeoside (8), quercetin-3,4’-di-O-glucoside (9) and rutine (10). Compounds 3, 4, 6, 8 and 10 displayed IC 50 ranging from 1.7 to 2.1 µM, and were the most active against the DENV-NS5 RdRp.
Keywords: Myrtaceae; Carpolepis laurifolia ; Dengue Virus; Flavonoids; Triterpenes. © 2014 ACG Publications. All rights reserved. |