title: Towards β-selectivity in functional estrogen receptor antagonists.
abstract: Based on the benzo[b]naphtho[1,2-d]furan and benzo[b]naphtho[1,2-d]thiophene frameworks, a series of ligands with different basic side chains (BSCs) has been synthesized and pharmacologically evaluated. Also, their binding modes have been modelled using docking techniques. It was found that the introduction of a BSC in these systems brings about a decrease of affinity for both estrogen receptors α and β in an in vitro competitive binding assay. However, two full antagonists of the estrogen receptor β (9c and 9f) have been discovered, with potency in the low micromolar concentration in a cell-based luciferase reporter assay, and completely devoid of activity against the α receptor at the same concentration range. Differences in the ERα/ERβ binding modes have also been rationalized with the help of molecular modelling techniques. This interesting functional profile could be used to elucidate the physiological role of each ER subtype.
authors: Departamento de Química, Facultad de Farmacia, Universidad CEU San Pablo, 28668-Boadilla del Monte, Madrid, Spain.
authors: Jose Juan
authors: JJ
authors: Rodríguez
authors: Kamila
authors: K
authors: Filipiak
authors: Maciej
authors: M
authors: Maslyk
authors: Jakub
authors: J
authors: Ciepielski
authors: Sebastian
authors: S
authors: Demkowicz
authors: Sonia
authors: S
authors: de Pascual-Teresa
authors: Sonsoles
authors: S
authors: Martín-Santamaría
authors: Beatriz
authors: B
authors: de Pascual-Teresa
authors: Ana
authors: A
authors: Ramos
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D008024:Ligands; D009281:Naphthalenes; D011960:Receptors, Estrogen; D013876:Thiophenes; C050000:benzo(b)naphtho(1,2-d)thiophene