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Structure‐Activity Relationship of 9-Methylstreptimidone, a Compound That Induces Apoptosis Selectively in Adult T-Cell Leukemia Cells

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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-κB 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,α-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.
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Keywords: 9-Methylstreptimidone; Adult T-cell leukemia; Apoptosis; Macrophage; Streptovitacin

Document Type: Research Article

Publication date: 2012-01-01

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