title: New scaffolds for the design of selective estrogen receptor modulators.
abstract: In the present work we report the synthesis of four new ER ligands which can be used as scaffolds for the introduction of the basic side chains necessary for antiestrogenic activity. Affinities and agonist/antagonist characterization of the ligands for both ERalpha and ERbeta have been determined in a competitive radioligand assay, and in an in vitro coactivator recruitment functional assay, respectively. Molecular modelling techniques have been used in order to rationalize the experimental results. Compound is reported as a novel ERbeta-agonist/ERalpha-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.
authors.affiliation: Departamento de Química, Facultad de Farmacia, Universidad San Pablo CEU, 28668-Boadilla del Monte, Madrid, Spain.
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
authors.forename: José-Juan
authors.initials: JJ
authors.lastname: Rodríguez
authors.forename: Sonia
authors.initials: S
authors.lastname: de Pascual-Teresa
authors.forename: Sandra
authors.initials: S
authors.lastname: Gordon
authors.forename: Martin
authors.initials: M
authors.lastname: Bengtsson
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garrido-Laguna
authors.forename: Belén
authors.initials: B
authors.lastname: Rubio-Viqueira
authors.forename: Pedro P
authors.initials: PP
authors.lastname: López-Casas
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol