Synthesis and biological evaluation of 7-hydroxy-3,4-diphenyl-1,2-dihydroisoquinolines as new 4-hydroxytamoxifen analogues.
A phenolic 3,4-diphenyl-1,2-dihydroisoquinoline derivative (4a) as a new 4-hydroxytamoxifen analogue and a related compound (4c) were synthesized from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (5a, c), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 4a,c and 5a,c, as well as 4b and 5b prepared previously, against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. The 3,4-diphenyl-1,2-dihydroisoquinoline derivatives (4a,c) and isoquinolin-4-ols (5a,b) were active against MCF-7 cells and were nearly equipotent to the corresponding nonphenolic compound (1a). The mechanism of the anti-proliferative activity of 4a-c against MCF-7 cells is discussed.
Kihara
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Ikeuchi
M
M
Yamauchi
A
A
Nukatsuka
M
M
Matsumoto
H
H
Toko
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D007624:KB Cells; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D007546:Isoquinolines; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene