Natural Product Research, Vol. 18, No. 1, February 2004, pp. 1–9 POLYPRENYL-HYDROQUINONES AND -FURANS FROM THREE MARINE SPONGES INHIBIT THE CELL CYCLE REGULATING PHOSPHATASE CDC25A ILKAY ERDOGAN-ORHAN a, *, BILGE SENER a , SALVATORE DE ROSA b , JULIA PEREZ-BAZ c , OLIVIER LOZACH d , MARYSE LEOST d , SERGEI RAKHILIN e and LAURENT MEIJER d,e,y a Department of Pharmacognosy, Faculty of Pharmacy, Gazi University 06330, Ankara, Turkey; b Istituto di Chimica Biomolecolare CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy; c Instituto Biomar S.A., Pol. Ind. Edificio CEEI, Mo ´d. 2.02, 24231 Onzonilla, Leo ´n Spain; d C.N.R.S Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France; e Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA (Received 24 November 2002; In final form 25 February 2002) The CDC25 phosphatases regulate the cell division cycle by controlling the activity of cyclin-dependent kinases. While screening for inhibitors of phosphatases among natural products we repeatedly found that some polyprenyl-hydroquinones and polyprenyl-furans (furanoterpenoids) (furospongins, furospinosulins) were potent CDC25 phosphatase inhibitors. These compounds were extracted, isolated and identified independently from three sponge species (Spongia officinalis, Ircinia spinulosa, Ircinia muscarum), collected at different locations in the Mediterranean Sea. The compounds were inactive on the Ser/Thr phosphatase PP2C- and on three kinases (CDK1, CDK5, GSK-3), suggesting that some potent and selective CDC25 phosphatase might be designed from these initial structures. Keywords: Polyprenyl-hydroquinones; Polyprenyl-furans; Cyclin-dependent kinases INTRODUCTION Protein phosphorylation probably represents the most common posttranslational mechanism used by cells to regulate the functions of their proteins. The phosphoryla- tion status of a protein is the result of a balance between the activities of protein kinases (phosphorylation) and protein phosphatases (dephosphorylation). Abnormalities in protein phosphorylation are observed in essentially all human pathologies, *E-mail: iorhan@gazi.edu.tr y Corresponding author. Tel.: 33 (0) 298292339. Fax: 33 (0) 298292342. E-mail: meijer@sb-roscoff.fr ISSN 1478-6419 print: ISSN 1029-2349 online ß 2004 Taylor & Francis Ltd DOI: 10.1080/1478641031000111534