Inhibitory effects of dehydrozingerone and related compounds on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation.
Dehydrozingerone, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, is half an analog of curcumin which is known to have anti-tumor activity. The anti-tumor promoting activity of dehydrozingerone was evaluated by determining the inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The concentration needed for 50% inhibition of the tumor promotion (IC50) of dehydrozingerone was similar to that of curcumin. To elucidate the structure-activity relationship on the anti-tumor promoting activity, dehydrozingerone, curcumin, isoeugenol, which has no carbonyl group in the side chain, benzalacetone, which is the basic structure of dehydrozingerone, o-dehydrozingerone, which is the ortho-hydroxyl substituted compound of dehydrozingerone, and their related compounds were investigated using the in vitro short-term assay on TPA-induced EBV-EA activation. o-Dehydrozingerone showed the most potent inhibitory effect in a series of tested dehydrozingerone derivatives and their related monosubstituted benzalacetones. This suggests that the occupation at both ortho positions of the hydroxyl group enhances the anti-tumor promoting activity. Isoeugenol inhibited the tumor promoting activity at a concentration of about one-third of the IC50 of dehydrozingerone. This indicates that the carbonyl group in the side chain has a negative impact on the anti-tumor promoting activity. The inhibitory effects of the carbon-carbon bond in the side chain were studied using benzylacetone with a single bond, benzalacetone with a double bond and 4-phenyl-3-butyn-2-one with a triple bond. 4-Phenyl-3-butyn-2-one inhibited the most potent activity followed by benzalacetone and benzylacetone.
Motohashi
N
N
Kobe Pharmaceutical University, Japan. motohashi@kobepharma-u.ac.jp
Yamagami
C
C
Tokuda
H
H
Konoshima
T
T
Okuda
Y
Y
Okuda
M
M
Mukainaka
T
T
Nishino
H
H
Saito
Y
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000956:Antigens, Viral / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000956:Antigens, Viral; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D013343:Styrenes; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate