The amide hydrogen of (-)-indolactam-V and benzolactam-V8's plays a critical role in protein kinase C binding and tumor-promoting activities.
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.
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan.
Y
Y
Nakagawa
K
K
Irie
Y
Y
Nakamura
H
H
Ohigashi
D000956:Antigens, Viral / Q000378:metabolism; D002273:Carcinogens / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D013481:Superoxides / Q000378:metabolism
D000956:Antigens, Viral; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D007211:Indoles; D007769:Lactams; D020033:Protein Isoforms; C113786:benzolactam V8-310; D013481:Superoxides; D006859:Hydrogen; C043969:indolactam V; D011493:Protein Kinase C