title: New bioactive halenaquinone derivatives from South Pacific marine sponges of the genus Xestospongia.
abstract: 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.
authors.affiliation: Laboratoire des Molécules de Communication et Adaptation des Micro-organismes, FRE 3206 CNRS, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Longeon
authors.forename: Brent R
authors.initials: BR
authors.lastname: Copp
authors.forename: Mélanie
authors.initials: M
authors.lastname: Roué
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Alexis
authors.initials: A
authors.lastname: Valentin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Petek
authors.forename: Cécile
authors.initials: C
authors.lastname: Debitus
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Bourguet-Kondracki
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects*; D011809:Quinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D047131:Xestospongia / Q000737:chemistry*; D015003:Yeasts / Q000201:enzymology
chemical_list: D000962:Antimalarials; D064801:Phospholipase A2 Inhibitors; D011809:Quinones; C430084:halenaquinone; D051231:Farnesyltranstransferase; D054467:Phospholipases A2