Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a Vanuatu marine sponge Pseudoceratina sp.

Marine Drugs
Nicolas LebouvierDominique Laurent

Abstract

As part of our search for new antimalarial drugs in South Pacific marine sponges, we have looked for inhibitors of Pfnek-1, a specific protein kinase of Plasmodium falciparum. On the basis of promising activity in a preliminary screening, the ethanolic crude extract of a new species of Pseudoceratina collected in Vanuatu was selected for further investigation. A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC(50) around 1.8 muM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC(50) = 12 muM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.

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Citations

May 11, 2011·Marine Drugs·Carolina Babosa Brito da MattaMagna Suzana Alexandre-Moreira
Nov 11, 2011·Marine Drugs·Danielle SkropetaAna Zivanovic
Dec 14, 2012·Future Medicinal Chemistry·Isabelle S LucetChristian Doerig
Feb 3, 2011·Pharmaceutical Biology·Edouard HnawiaBruno Fogliani
Jul 27, 2012·Immunopharmacology and Immunotoxicology·Luciano de Sousa ChavesJand-Venes Rolim Medeiros
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Dec 18, 2014·Journal of Natural Products·Stephanie J ConnStephen Chamberland
Jul 15, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Haruka FukamachiHirotaka Kuwata
Dec 23, 2016·Chemical Biology & Drug Design·Komal AnjumSyed Shams Ul Hassan
Aug 18, 2012·Chemistry & Biodiversity·Luke ManiCécile Debitus
Nov 13, 2018·Current Medicinal Chemistry·Chao Li, Dayong Shi
Apr 8, 2011·Natural Product Reports·Zhong Jin
Nov 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chantalle MoolmanLesetja J Legoabe
May 18, 2018·Journal of Medicinal Chemistry·Diego González CabreraKelly Chibale

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Methods Mentioned

BETA
column chromatography

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