Hybrids of 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1) and 3beta-methoxyserrat-14-en-21beta-ol (PJ-2) and various anti-oxidants as cancer chemopreventive agents.
3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol (2) and their conjugates with curcumin, kojic acid, quercetin, and baicalein (3-18), as well as new analogs (19-24) derived from 1 and 2, were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 16 (IC50=330 mol ratio/32 pmol/TPA), 9 (IC50=335), 10 (IC50=338), and 15 (IC50=350) were stronger than those of the other compounds and the positive control, oleanolic acid (IC50=449). Compounds 15 and 16, which are conjugates of one molecule each of 1 or 2 and quercetin, inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
Tsujii
Hiroko
H
Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Yamada
Takeshi
T
Kajimoto
Tetsuya
T
Tanaka
Reiko
R
Tokuda
Harukuni
H
Hasegawa
Junya
J
Hamashima
Yoshio
Y
Node
Manabu
M
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000201:enzymology; D004854:Herpesvirus 4, Human; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000517:prevention & control*; D011753:Pyrones / Q000737:chemistry; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
C492953:3beta-methoxyserrat-14-en-21beta-ol; D000956:Antigens, Viral; D000970:Antineoplastic Agents; D000975:Antioxidants; D011753:Pyrones; D014315:Triterpenes; C011890:kojic acid; D054303:HIV Reverse Transcriptase; D013755:Tetradecanoylphorbol Acetate