Synthesis, conformational analysis, and biological evaluation of 1-hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes.

Abstract

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 microM. These results suggest that 5 could be useful for the functional analysis of novel PKC isozymes.

• Authors: Ryo C Yanagita, Yu Nakagawa, Nobuhiro Yamanaka, Kaori Kashiwagi, Naoaki Saito, Kazuhiro Irie
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 1 Pg. 46-56 (Jan 10 2008) ISSN: 0022-2623 [Print] United States
• PMID: 18072722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-hexylindolactam-V10
• Enzyme Activators
• Indoles
• Isoenzymes
• Lactams
• indolactam V
• Protein Kinase C

Topics

• Cell Membrane (enzymology)
• Enzyme Activators (chemical synthesis, chemistry, pharmacology)
• HeLa Cells
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Isoenzymes (genetics, metabolism)
• Lactams (chemical synthesis, chemistry, pharmacology)
• Models, Molecular
• Molecular Conformation
• Mutation
• Protein Binding
• Protein Kinase C (genetics, metabolism)
• Protein Transport
• Structure-Activity Relationship