Synthesis and biological activity of olomoucine II |
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| Authors: | Krystof Vladimír Lenobel René Havlícek Libor Kuzma Marek Strnad Miroslav |
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| Affiliation: | 1. Laboratory of Growth Regulators, Palacký University and Institute of Experimental Botany, Šlechtitelů 11, 783 71 Olomouc, Czech Republic;2. Isotope Laboratory, Institute of Experimental Botany, Czech Academy of Sciences, Vı́deňská 1083, 14220 Prague 4, Czech Republic;3. Institute of Microbiology, Czech Academy of Sciences, Vı́deňská 1083, 14220 Prague 4, Czech Republic;1. Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong;2. Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, China;3. Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China;4. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong;5. Institute of Chinese Medical Sciences, University of Macau, Macau, China;6. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong;7. Department of Physiology, The University of Hong Kong, Hong Kong;1. Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy;2. Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, Baltimore, MD, 333 Cassell Drive, Baltimore, MD 21224, USA;3. Department of Chemistry & Biochemistry, College of Science and Mathematics, Rowan University 201 Mullica Hill Rd, Glassboro, NJ 08028, USA;4. Department of Biomedical & Translational Sciences, College of Science and Mathematics, Rowan University 201 Mullica Hill Rd, Glassboro, NJ 08028, USA;5. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy;6. Recordati S.p.A., Drug Discovery, Via Civitali 1, 20148 Milano, Italy;7. Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino (NEUROFARBA), Sezione di Farmacologia e Tossicologia, Universita'' degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy;1. Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China;2. Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China;3. Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China;4. Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China;5. Department of Pathology, Anhui Provincial Hospital, Hefei 230001, China;6. Department of Dermatology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China;1. Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraβe 55, 38106 Braunschweig, Germany;2. Technische Universität Braunschweig, Center of Pharmaceutical Engineering (PVZ), Franz-Liszt-Straβe 35A, D-38106 Braunschweig, Germany;3. ProQinase GmbH, Breisacher Straβe 117, 79106 Freiburg, Germany |
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| Abstract: | Based on our previous experiences with synthesis of purines, novel 2,6,9-trisubstituted purine derivatives were prepared and assayed for the ability to inhibit CDK1/cyclin B kinase. One of newly synthesized compounds designated as olomoucine II, 6-[(2-hydroxybenzyl)amino]-2-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine, displays 10 times higher inhibitory activity than roscovitine, potent and specific CDK1 inhibitor. Olomoucine II in vitro cytotoxic activity exceeds purvalanol A, the most potent CDK inhibitor, as it kills the CEM cells with IC(50) value of 3.0 microM. |
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