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

被引：19

作者：

Nakagawa, Y

Irie, K ^{[1
]}

Nakamura, Y

Ohigashi, H

机构：

[1] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Sakyo Ku, Kyoto 6068502, Japan

[2] Nagoya Univ, Grad Sch Bioagr Sci, Lab Food & Biodynam, Nagoya, Aichi 4648601, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 05期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/S0960-894X(01)00047-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2001 Published by Elsevier Science Ltd.

引用

页码：723 / 728

页数：6

共 30 条

[1] ENZYMATIC MECHANISMS OF SUPEROXIDE PRODUCTION
CROSS, AR
JONES, OTG
[J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1057 (03) : 281 - 298
[2] ENDO Y, 1982, CHEM PHARM BULL, V30, P3457
[3] Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cδ by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation
Endo, Y
Takehana, S
Ohno, M
Driedger, PE
Stabel, S
Mizutani, MY
Tomioka, N
Itai, A
Shudo, K
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (09) : 1476 - 1496
[4] Endo Y, 1997, CHEM PHARM BULL, V45, P424
[5] Synthesis, conformation, and biological activity of teleocidin mimics, benzolactams. A clarification of the conformational flexibility problem in structure-activity studies of teleocidins
Endo, Y
Ohno, M
Hirano, M
Itai, A
Shudo, K
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (08) : 1841 - 1855
[6] SYNTHESIS AND STEREOCHEMISTRY OF INDOLACTAM-V, AN ACTIVE FRAGMENT OF TELEOCIDINS - STRUCTURAL REQUIREMENTS FOR TUMOR-PROMOTING ACTIVITY
ENDO, Y
SHUDO, K
ITAI, A
HASEGAWA, M
SAKAI, S
[J]. TETRAHEDRON, 1986, 42 (21) : 5905 - 5924
[7] Hurley JH, 1997, PROTEIN SCI, V6, P477
[8] Synthesis and tumor-promoting activities of 12-epi-phorbol-12, 13-dibutyrate
Irie, K
Nakahara, A
Ikawa, Y
Tanaka, M
Nakagawa, Y
Nakamura, Y
Ohigashi, H
Wender, PA
[J]. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2000, 64 (11) : 2429 - 2436
[9] Molecular basis for protein kinase C isozyme-selective binding: The synthesis, folding, and phorbol ester binding of the cysteine-rich domains of all protein kinase C isozymes
Irie, K
Oie, K
Nakahara, A
Yanai, Y
Ohigashi, H
Wender, PA
Fukuda, H
Konishi, H
Kikkawa, U
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (36) : 9159 - 9167
[10] THE EPSTEIN-BARR VIRUS EARLY ANTIGEN INDUCING INDOLE ALKALOIDS, (-)-INDOLACTAM-V AND ITS RELATED-COMPOUNDS, PRODUCED BY ACTINOMYCETES
IRIE, K
HIROTA, M
HAGIWARA, N
KOSHIMIZU, K
HAYASHI, H
MURAO, S
TOKUDA, H
ITO, Y
[J]. AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 1984, 48 (05): : 1269 - 1274

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