title: Structure-activity relationships in 1,4-benzodioxan-related compounds. 11. (1) reversed enantioselectivity of 1,4-dioxane derivatives in α1-adrenergic and 5-HT1A receptor binding sites recognition.
abstract: 5-HT(1A) receptor and α(1)-adrenoreceptor (α(1)-AR) binding sites recognized by the 1,4-dioxanes 2-4 display reversed stereochemical requirements. (S)-2 proved to be a potent 5-HT(1A) receptor agonist highly selective over α(1)-AR subtypes. Chirality influenced the anticancer activity of 3 and 4 in human prostate cancer cells (PC-3): (R)-4, eutomer at the α(1d)-AR subtype, was the most potent. The decreased effect of 4 and (R)-4 in α(1d)-AR silenced PC-3 cells confirmed that their anticancer activity was α(1d)-AR-dependent.
authors.affiliation: Medicinal Chemistry Unit, School of Pharmacy,  University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bonifazi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Bello
authors.forename: Yogita
authors.initials: Y
authors.lastname: Farande
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Massimo
authors.initials: M
authors.lastname: Nabissi
authors.forename: Valerio
authors.initials: V
authors.lastname: Farfariello
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Elena
authors.initials: E
authors.lastname: Poggesi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Leonardi
authors.forename: Sergio
authors.initials: S
authors.lastname: Menegon
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; D044263:Receptors, Serotonin, 5-HT1; D044282:Receptor, Serotonin, 5-HT1A; C527681:1,4-benzodioxan