The amide hydrogen of (-)-indolactam-V and benzolactam-V8's plays a critical role in protein kinase C binding and tumor-promoting activities.

Abstract

To investigate the role of the amide hydrogen of (-)-indolactam-V (1) and benzolactam-V8's on protein kinase C (PKC) binding and tumor promotion, 8-decylbenzolactone-V8 (6), a new lactone analogue of 8-decylbenzolactam-V8 (4), was synthesized from 2-nitrophenylpyruvic acid (7) in 11 steps. The PKC binding ability and tumor-promoting activities in vitro of 6 were much lower than those of 1 and 4, suggesting that the amide hydrogen of 1 and benzolactam-V8's plays a critical role in tumor promotion. However, it is noteworthy that 6 showed significant selectivity in the PKC isozyme surrogate binding.

• Authors: Y Nakagawa, K Irie, Y Nakamura, H Ohigashi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 11 Issue 5 Pg. 723-8 (Mar 12 2001) ISSN: 0960-894X [Print] England
• PMID: 11266178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Carcinogens
• Epstein-Barr virus early antigen
• Indoles
• Lactams
• Protein Isoforms
• benzolactam V8-310
• Superoxides
• Hydrogen
• indolactam V
• Protein Kinase C

Topics

• Antigens, Viral (metabolism)
• Carcinogens (chemistry, metabolism, pharmacology)
• Humans
• Hydrogen (chemistry)
• Indoles (chemistry, metabolism, pharmacology)
• Kinetics
• Lactams (chemistry, metabolism, pharmacology)
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Protein Binding
• Protein Isoforms (metabolism)
• Protein Kinase C (chemistry, metabolism)
• Radioligand Assay
• Superoxides (metabolism)