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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.
AuthorsMasatoshi Takeiri, Eisuke Ota, Shigeru Nishiyama, Hiromasa Kiyota, Kazuo Umezawa
JournalOncology research (Oncol Res) Vol. 20 Issue 1 Pg. 7-14 ( 2012) ISSN: 0965-0407 [Print] United States
PMID23035360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 4,alpha-diepi-streptovitacin A
  • Lipopolysaccharides
  • NF-kappa B
  • Piperidones
  • Nitric Oxide
  • 9-methylstreptimidone
  • streptovitacin A
  • Cycloheximide
Topics
  • Animals
  • Apoptosis (drug effects)
  • Cells, Cultured
  • Cycloheximide (analogs & derivatives, chemistry, pharmacology)
  • Humans
  • Jurkat Cells
  • Leukemia, T-Cell (drug therapy)
  • Lipopolysaccharides (pharmacology)
  • Macrophages (drug effects, metabolism)
  • Mice
  • NF-kappa B (drug effects, metabolism)
  • Nitric Oxide (metabolism)
  • Piperidones (chemistry, pharmacology)
  • Structure-Activity Relationship

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