Alisiaquinones and alisiaquinol, dual inhibitors of Plasmodium falciparum enzyme targets from a New Caledonian deep water sponge.
Four new meroterpenes, alisiaquinones A-C (1-3) and alisiaquinol (4), were isolated from a New Caledonian deep water sponge. Their structures and relative stereochemistry were elucidated by spectroscopic data analysis. They are related to xestoquinone, but showed unusual substitution on a tetrahydrofuran junction. They displayed micromolar range activity on two enzymatic targets of importance for the control of malaria, the plasmodial kinase Pfnek-1 and a protein farnesyl transferase, as well as on different chloroquine-sensitive and -resistant strains of Plasmodium falciparum. Alisiaquinone C displayed a submicromolar activity on P. falciparum and a competitive selectivity index on the different plasmodial strains.
UMS Pierre Fabre-CNRS 2587 and 2646, Institut de Sciences et Technologies du Médicament de Toulouse, 31432 Toulouse, France.
Denis
D
Desoubzdanne
Laurence
L
Marcourt
Roselyne
R
Raux
Séverine
S
Chevalley
Dominique
D
Dorin
Christian
C
Doerig
Alexis
A
Valentin
Frédéric
F
Ausseil
Cécile
C
Debitus
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D008386:Marine Biology; D015394:Molecular Structure; D000072380:NIMA-Related Kinase 1; D009510:New Caledonia; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects / Q000201:enzymology*; D011161:Porifera / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000962:Antimalarials; D018797:Cell Cycle Proteins; D013729:Terpenes; C531419:alisiaquinol; C531420:alisiaquinone A; C531421:alisiaquinone B; C531422:alisiaquinone C; D002738:Chloroquine; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases