Synthesis of N-chlorosulfonyl dicyclohexylamine as a potent inhibitor for spermidine synthase and its effects on human leukemia Molt4B cells.
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.
D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003514:Cyclohexylamines / Q000138:chemical synthesis*; D006131:Growth Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D009696:Nucleic Acids / Q000096:biosynthesis; D011073:Polyamines / Q000378:metabolism; D014176:Protein Biosynthesis; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors*; D014166:Transferases / Q000037:antagonists & inhibitors*
D003514:Cyclohexylamines; D006131:Growth Inhibitors; D009696:Nucleic Acids; D011073:Polyamines; C051108:N-chlorosulfonyl dicyclohexylamine; D014166:Transferases; D011436:Spermidine Synthase