Chemical and biological explorations of the electrophilic reactivity of the bioactive marine natural product halenaquinone with biomimetic nucleophiles.
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).
Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Jiayi
J
Wang
Marie-Lise
ML
Bourguet-Kondracki
Arlette
A
Longeon
Joëlle
J
Dubois
Alexis
A
Valentin
Brent R
BR
Copp
D000111:Acetylcysteine / Q000737:chemistry; D000818:Animals; D001516:Bees / Q000201:enzymology; D040761:Biomimetic Materials / Q000737:chemistry*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D064801:Phospholipase A2 Inhibitors; D011809:Quinones; C430084:halenaquinone; D051231:Farnesyltranstransferase; D054467:Phospholipases A2; D000111:Acetylcysteine