Alisiaquinones and alisiaquinol, dual inhibitors of Plasmodium falciparum enzyme targets from a New Caledonian deep water sponge.

Abstract

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.

• Authors: Denis Desoubzdanne, Laurence Marcourt, Roselyne Raux, Séverine Chevalley, Dominique Dorin, Christian Doerig, Alexis Valentin, Frédéric Ausseil, Cécile Debitus
• Journal: Journal of natural products (J Nat Prod) Vol. 71 Issue 7 Pg. 1189-92 (Jul 2008) ISSN: 1520-6025 [Electronic] United States
• PMID: 18512987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Cell Cycle Proteins
• Terpenes
• alisiaquinol
• alisiaquinone A
• alisiaquinone B
• alisiaquinone C
• Chloroquine
• Alkyl and Aryl Transferases
• p21(ras) farnesyl-protein transferase
• NEK1 protein, human
• NIMA-Related Kinase 1
• Protein Serine-Threonine Kinases

Topics

• Alkyl and Aryl Transferases (antagonists & inhibitors)
• Animals
• Antimalarials (chemistry, isolation & purification, pharmacology)
• Cell Cycle Proteins (antagonists & inhibitors)
• Chloroquine (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance (drug effects)
• Female
• Humans
• Malaria (drug therapy)
• Marine Biology
• Molecular Structure
• NIMA-Related Kinase 1
• New Caledonia
• Plasmodium falciparum (classification, drug effects, enzymology)
• Porifera (chemistry)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Terpenes (chemistry, isolation & purification, pharmacology)