manoalide and halenaquinone

The electrophilic reactivity of the bioactive marine sponge natural product halenaquinone has been investigated by reaction with the biomimetic nucleophiles N-acetyl-L-cysteine and N(α)-acetyl-L-lysine. While cysteine reacted at the vacant quinone positions C-14 and C-15, lysine was found to react preferentially at the keto-furan position C-1. A small library of analogues was prepared by reaction of halenaquinone with primary amines, and evaluated against a range of biological targets including phospholipase A(2), farnesyltransferases (FTases) and Plasmodium falciparum. Geranylamine analogue 11 exhibited the most potent activity towards FTases (IC(50) 0.017-0.031 μM) and malaria (IC(50) 0.53-0.62 μM).

Topics: Acetylcysteine; Animals; Bees; Biomimetic Materials; Farnesyltranstransferase; Humans; Phospholipase A2 Inhibitors; Phospholipases A2; Plasmodium falciparum; Porifera; Quinones

Bioassay-directed fractionation of South Pacific marine sponges of the genus Xestospongia has led to the isolation of a number of halenaquinone-type polyketides, including two new derivatives named xestosaprol C methylacetal 7 and orhalquinone 8. Chemical characterization of these two new compounds was achieved by extensive 1D and 2D NMR spectroscopic studies. Evaluation of anti-phospholipase A(2), anti-farnesyltransferase and antiplasmodial activities of this series is presented and structure/activity relationships are discussed. Orhalquinone 8 displayed a significant inhibition of both human and yeast farnesyltransferase enzymes, with IC(50) value of 0.40 microM and was a moderate growth inhibitor of Plasmodium falciparum.

Topics: Animals; Antimalarials; Cell Survival; Chlorocebus aethiops; Farnesyltranstransferase; Humans; Malaria, Falciparum; Phospholipase A2 Inhibitors; Phospholipases A2; Plasmodium falciparum; Quinones; Structure-Activity Relationship; Vero Cells; Xestospongia; Yeasts