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 | Masatoshi Takeiri, Eisuke Ota, Shigeru Nishiyama, Hiromasa Kiyota, Kazuo Umezawa |
Journal | Oncology research
(Oncol Res)
Vol. 20
Issue 1
Pg. 7-14
( 2012)
ISSN: 0965-0407 [Print] United States |
PMID | 23035360
(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
|