title: Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.
abstract: We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimidone is poorly obtained from the producing microorganism and difficult to synthesize. Therefore, in the present research, we studied the structure-activity relationship to look for new selective inhibitors. We found that the structure of the unsaturated hydrophobic portion of 9-methylstreptimidone was essential for the inhibition of LPS-induced NO production. Among the 9-methylstreptimidone-related compounds tested, (+/-)-4,alpha-diepi-streptovitacin A inhibited NO production in macrophage-like cells as potently as 9-methylstreptimidone and without cellular toxicity. Moreover, this compound selectively induced apoptosis in adult T-cell leukemia MT-1 cells.
authors.affiliation: Center for Chemical Biology, Faculty of Science and Technology, Keio University, Yokohama, Japan. take_azalee2877@yahoo.co.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeiri
authors.forename: Eisuke
authors.initials: E
authors.lastname: Ota
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kiyota
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010881:Piperidones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C576417:4,alpha-diepi-streptovitacin A; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010881:Piperidones; D009569:Nitric Oxide; C008497:9-methylstreptimidone; C005257:streptovitacin A; D003513:Cycloheximide