Cancer chemopreventive effect of quassinoid derivatives. Introduction of side chain to shinjulactone C for enhancement of inhibitory effect on Epstein-Barr virus activation.
A series of shinjulactone C (1) derivatives (2-8) were synthesized and evaluated for their anti-tumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The succinate and 3',3'-dimethylsuccinate derivatives of 1 exhibited higher inhibitory effects than 1. From the point of view of structure-activity relationships, the succinate derivatives (2, 4) demonstrated better potency than the glutarate derivatives (3, 5-8). As substituted moieties of 3'-position became bulky, the inhibitory effects of the glutarate derivatives (7, 8) significantly decreased.
Tamura
Sadaaki
S
Department of Interdisciplinary Studies of Natural Environment, Faculty of Integrated Arts and Sciences, Hiroshima University, 739-8521, Higashi-Hiroshima, Japan.
Fukamiya
Narihiko
N
Okano
Masayoshi
M
Tokuda
Harukuni
H
Aoi
Wataru
W
Mukainaka
Teruo
T
Nishino
Hoyoku
H
Tagahara
Kiyoshi
K
Koike
Kazuo
K
D000956:Antigens, Viral / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D020031:Epstein-Barr Virus Infections / Q000517:prevention & control*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D036702:Quassins / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000187:drug effects*
D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; C033305:Epstein-Barr virus early antigen; D007783:Lactones; D036702:Quassins; D013755:Tetradecanoylphorbol Acetate