Structure-activity relationships of (1′S)-1′-acetoxychavicol acetate, a major constituent of a southeast Asian condiment plant Languas galanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation

被引:34
作者
Murakami, A
Toyota, K
Ohura, S
Koshimizu, K
Ohigashi, H [1 ]
机构
[1] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Kyoto 6068502, Japan
[2] Kinki Univ, Fac Biol Oriented Sci & Technol, Dept Biotechnol Sci, Wakayama 6496493, Japan
关键词
1 '-acetoxychavicol acetate; Epstein-Barr virus; structure-activity relationships; chemoprevention; teleocidin B-4;
D O I
10.1021/jf990528r
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
The structure-activity relationships of(1'S)-1'-acetoxychavicol acetate (ACA), a cancer chemopreventive agent of food origin, were investigated in an inhibitory test of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells. Through a test of 16 derivatives, the structural factors regulating activity were found to be as follows: (1) the absolute configuration at the 1'-position does not affect activity; (2) hydrogenation of the terminal methylene group abolishes activity; (3) both the phenolic and alcoholic hydroxyl groups are compulsorily acetylated, and it is necessary that the former is oriented only at the position para to the side chain; (4) an additional acetoxyl group is allowed to locate at the ortho or meta position; and (5) substitution of the hydrogen atom at the 1'-position by a methyl group reduces activity. Upon esterase blockade in Raji cells, (1'R,S)-ACA suppressed EBV activation, the extent of which was the same as tested in the control, suggesting that ACA bearing two acetoxyl groups is an intracellular structure prerequisite for activity exhibition. The present study suggests that nucleophilic attack to the 3'-position is important and involved in the interaction of ACA with an unidentified target molecule(s) participating in the process of EBV activation.
引用
收藏
页码:1518 / 1523
页数:6
相关论文
共 25 条
[1]   THE EPSTEIN-BARR VIRUS EARLY ANTIGEN INDUCING INDOLE ALKALOIDS, (-)-INDOLACTAM-V AND ITS RELATED-COMPOUNDS, PRODUCED BY ACTINOMYCETES [J].
IRIE, K ;
HIROTA, M ;
HAGIWARA, N ;
KOSHIMIZU, K ;
HAYASHI, H ;
MURAO, S ;
TOKUDA, H ;
ITO, Y .
AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 1984, 48 (05) :1269-1274
[2]   EPSTEIN-BARR VIRUS EARLY ANTIGEN INDUCING ACTIVITY OF 14-O-DERIVATIVES OF (-)-INDOLACTAM-V [J].
IRIE, K ;
HAGIWARA, N ;
KOSHIMIZU, K ;
TOKUDA, H ;
ITO, Y ;
HAYASHI, H ;
MURAO, S .
AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 1985, 49 (05) :1441-1446
[3]  
ITOKAWA H, 1987, Planta Medica, V53, P32, DOI 10.1055/s-2006-962611
[4]  
Jacquat C., 1990, Plants from the Markets of Thailand, V1st ed.
[5]  
KENSLER T W, 1989, P233
[6]   EVOLUTION OF TUMORS AND THE IMPACT OF MOLECULAR ONCOLOGY [J].
KLEIN, G ;
KLEIN, E .
NATURE, 1985, 315 (6016) :190-195
[7]   Prevention by 1′-acetoxychavicol acetate of the induction but not growth of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet [J].
Kobayashi, Y ;
Nakae, D ;
Akai, H ;
Kishida, H ;
Okajima, E ;
Kitayama, W ;
Denda, A ;
Tsujiuchi, T ;
Murakami, A ;
Koshimizu, K ;
Ohigashi, H ;
Konishi, Y .
CARCINOGENESIS, 1998, 19 (10) :1809-1814
[8]   1'-ACETOXYCHAVICOL ACETATE AS A POTENT INHIBITOR OF TUMOR PROMOTER-INDUCED EPSTEIN-BARR-VIRUS ACTIVATION FROM LANGUAS-GALANGA, A TRADITIONAL THAI CONDIMENT [J].
KONDO, A ;
OHIGASHI, H ;
MURAKAMI, A ;
SURATWADEE, J ;
KOSHIMIZU, K .
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 1993, 57 (08) :1344-1345
[9]  
Kumar S., 1998, Indian Journal of Cancer, V35, P47
[10]  
LEONCINI L, 1993, INT J CANCER, V53, P898