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

Bioorg Med Chem Lett. 2001 Mar 12;11(5):723-8. doi: 10.1016/s0960-894x(01)00047-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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