title: Identification of a series of tetrahydroisoquinoline derivatives as potential therapeutic agents for breast cancer.
abstract: A series of tetrahydroisoquinoline-N-phenylamide derivatives were designed, synthesized, and tested for their relative binding affinities, and antagonistic activities against estrogen receptor (ER). Compound 1f (relative binding affinity, RBA=5) showed higher binding affinity than tamoxifen (RBA=1), a potent ER antagonist and currently being used for breast cancer therapy. Compound 1f also exerted optimal antagonistic activity against ER in reporter and cell proliferation assays. Interestingly, compound 1j, which only has a minor agonistic effect against ER, acted as a progesterone receptor (PR) antagonist and exerted agonistic activity against AP-1 through ER pathway. Our results show that these new compounds can be employed as leading pharmacophore for further development of potent selective ER and/or PR modulators or antagonists.
authors.affiliation: Department of Chemistry, College of Science, National Kaohsiung Normal University, Kaohsiung 824, Taiwan, ROC. t3136@nknucc.nknu.edu.tw
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Lin
authors.forename: Martin K
authors.initials: MK
authors.lastname: Safo
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Abraham
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D017930:Genes, Reporter; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D044005:Tetrahydroisoquinolines