TY - JOUR
T1 - Cancer preventive agents 11. Novel analogs of dimethyl dicarboxylate biphenyl as potent cancer chemopreventive agents
AU - Hung, Hsin Yi
AU - Nakagawa-Goto, Kyoko
AU - Tokuda, Harukuni
AU - Iida, Akira
AU - Suzuki, Nobutaka
AU - Morris-Natschke, Susan L.
AU - Lee, Kuo Hsiung
N1 - Funding Information:
This study was supported in part by NIH grant CA17625-32 from the National Cancer Institute awarded to K. H. Lee, and also in part by the Department of Health Cancer Research Center of Excellence (DOH-100-TD-C-111-05). The authors alone are responsible for the content and writing of the paper.
PY - 2012/1
Y1 - 2012/1
N2 - Context: Dimethyl dicarboxylate biphenyl (DDB) is a clinically used hepatoprotectant and has also been found to have chemopreventive activity. Materials and methods: Sixteen novel analogs (5-20) were designed, synthesized, and evaluated for their cancer preventive activity. The 2,2′-bismethyl ester (5-18) and ether (19, 20) DDB analogs were synthesized by insertion of various linear alkyl, short fatty acid, polar, and aromatic groups. All synthesized analogs were evaluated in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein Barr virus early antigen (EBA-EA) activation assay. Three of the most potent compounds were also tested for inhibitory effects on skin tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Results: Compound 19 with bisprenyl ethers had the most significant cancer preventive activity (100% inhibition of activation at 1×10 3 mol ratio/TPA, 78.4%, 49.7%, and 10.9% inhibition at 5×10 2, 1×10 2, 1×10mol ratio/TPA, respectively) in vitro. Compound 19 also exhibited a remarkable inhibitory effect on skin tumor promotion in the in vivo two-stage mouse-skin carcinogenesis test. Discussion and conclusions: Thus, DDB analog 19 could be a valuable candidate as a cancer preventive agent or as a lead for the development of new antitumor promoter drugs.
AB - Context: Dimethyl dicarboxylate biphenyl (DDB) is a clinically used hepatoprotectant and has also been found to have chemopreventive activity. Materials and methods: Sixteen novel analogs (5-20) were designed, synthesized, and evaluated for their cancer preventive activity. The 2,2′-bismethyl ester (5-18) and ether (19, 20) DDB analogs were synthesized by insertion of various linear alkyl, short fatty acid, polar, and aromatic groups. All synthesized analogs were evaluated in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein Barr virus early antigen (EBA-EA) activation assay. Three of the most potent compounds were also tested for inhibitory effects on skin tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Results: Compound 19 with bisprenyl ethers had the most significant cancer preventive activity (100% inhibition of activation at 1×10 3 mol ratio/TPA, 78.4%, 49.7%, and 10.9% inhibition at 5×10 2, 1×10 2, 1×10mol ratio/TPA, respectively) in vitro. Compound 19 also exhibited a remarkable inhibitory effect on skin tumor promotion in the in vivo two-stage mouse-skin carcinogenesis test. Discussion and conclusions: Thus, DDB analog 19 could be a valuable candidate as a cancer preventive agent or as a lead for the development of new antitumor promoter drugs.
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U2 - 10.3109/13880209.2011.608078
DO - 10.3109/13880209.2011.608078
M3 - Article
C2 - 22196579
AN - SCOPUS:84555196635
SN - 1388-0209
VL - 50
SP - 18
EP - 24
JO - Pharmaceutical Biology
JF - Pharmaceutical Biology
IS - 1
ER -