Synthesis, Conformational Analysis, and Biological Evaluation of 1-Hexylindolactam-V10 as a Selective Activator for Novel Protein Kinase C Isozymes

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• 作者：Ryo C. Yanagita ; Yu Nakagawa ; Nobuhiro Yamanaka ; Kaori Kashiwagi ; Naoaki Saito ; Kazuhiro Irie
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：January 10, 2008
• 年：2008
• 卷：51
• 期：1
• 页码：46 - 56
• 全文大小：1705K
• 年卷期：v.51,no.1(January 10, 2008)
• ISSN：1520-4804

文摘

Conventional and novel protein kinase C (PKC) isozymes are the main targets of tumor promoters. We developed 1-hexylindolactam-V10 (5) as a selective activator for novel PKC isozymes that play important roles in various cellular processes related to tumor promotion, ischemia−reperfusion injury in the heart, and Alzheimer’s disease. The compound existed as a mixture of three conformers. The trans-amide restricted analogues of 5 (14 and 15) hardly bound to PKC isozymes, suggesting that the active conformation of 5 could be that with a cis-amide. Compound 5 selectively translocated novel PKC isozymes over conventional PKC isozymes in HeLa cells at 0.1–1 μM. These results suggest that 5 could be useful for the functional analysis of novel PKC isozymes.