Coscinosulfate, a CDC25 phosphatase inhibitor from the sponge Coscinoderma mathewsi.
The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho-amino acids of cyclin-dependent kinases, a major family of cell cycle regulators. CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer activity. While screening through a collection of natural products derived from marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate 1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi, along with 4. The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM).
Loukaci
A
A
Laboratoire de Chimie des Substances Naturelles, Muséum d'Histoire Naturelle, associé au CNRS, Paris, France.
Le Saout
I
I
Samadi
M
M
Leclerc
S
S
Damiens
E
E
Meijer
L
L
Debitus
C
C
Guyot
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D012717:Sesquiterpenes; D013729:Terpenes; C449079:coscinosulfate; D020687:cdc25 Phosphatases