Synthesis of N-chlorosulfonyl dicyclohexylamine as a potent inhibitor for spermidine synthase and its effects on human leukemia Molt4B cells |
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| Authors: | K Nakashima T Tsukada H Hibasami S Maekawa |
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| Affiliation: | 1. Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain;2. Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain;3. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;4. CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain;1. Department of Microbiology and Excellence Research Laboratory on Natural Products, Faculty of Science and Natural Products Research Center of Excellence, Prince of Songkla University, Thailand;2. Department of Microbiology, Monash University, Clayton, Victoria, Australia;3. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia;4. Murdoch Children''s Research Institute, Royal Children''s Hospital, Parkville, Victoria, Australia |
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| Abstract: | N-Chlorosulfonyl dicyclohexylamine (CSD) was synthesized as a potent inhibitor of spermidine synthase and analyzed for antiproliferative effects on leukemic cells. The compound specifically inhibited spermidine synthase in a competitive mode with the substrate putrescine (Ki, 1.8 X 10(-7) M). When human leukemia Molt4B cells were cultured in the presence of the inhibitor, the intracellular level of spermidine and the rate of cell proliferation were markedly depressed. In these polyamine depleted and growth retarded cells the synthesis of protein, but not of DNA or RNA, was found to be significantly diminished. |
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