Potential cancer chemopreventive activity of simple isoquinolines, 1-benzylisoquinolines, and protoberberines.
Seventeen simple isoquinolines, 15 1-benzylisoquinolines, and 19 protoberberines were tested for their inhibitory activities against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among the tested alkaloids, the inhibitory activity of all 1-benzylisoquinolines and 11 protoberberines was higher than that of beta-carotene. The 1-benzylisoquinolines 19, 21, 22, 29, and 34 and protoberberines 41, 47-49, 51, 52, and 55 showed potent inhibitory effects on EBV-EA induction (96-100% inhibition at 1 x 10(3) mol ratio/TPA). These alkaloids were more active than the naturally occurring alkaloids, 23, 25, 33, 53, and 54. In addition, fifteen simple isoquinolines, eighteen 1-benzylisoquinolines and eight protoberberines were evaluated with respect to their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. Nine simple isoquinolines, ten 1-benzylisoquinolines, and four protoberberines were more potent than alpha-tocopherol, and four 1-benzylisoquinolines, 20 and 28-30, exhibited potent activities (SC50 4.5-5.8 microM). Their activities were higher than the naturally occurring alkaloids, 23, 25, and 33. Therefore, some of the isoquinoline alkaloids indicating the high activity on both assays may be potentially valuable cancer chemopreventive agents. Structure-activity relationships are discussed for both tests.
Cui
Wenhua
W
Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Kobe 658-8558, Japan.
Iwasa
Kinuko
K
Tokuda
Harukuni
H
Kashihara
Akiko
A
Mitani
Yosuke
Y
Hasegawa
Tomoko
T
Nishiyama
Yumi
Y
Moriyasu
Masataka
M
Nishino
Hoyoku
H
Hanaoka
Miyoji
M
Mukai
Chisato
C
Takeda
Kazuyoshi
K
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000956:Antigens, Viral / Q000187:drug effects / Q000378:metabolism; D001600:Berberine Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000633:toxicity
D016588:Anticarcinogenic Agents; D000956:Antigens, Viral; D001600:Berberine Alkaloids; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D016166:Free Radical Scavengers; D005609:Free Radicals; D007546:Isoquinolines; C009090:protoberberine; D013755:Tetradecanoylphorbol Acetate