title: Novel highly potent and selective nonsteroidal aromatase inhibitors: synthesis, biological evaluation and structure-activity relationships investigation.
abstract: In further pursuing our search for potent and selective aromatase inhibitors, a new series of molecules was designed and synthesized, exploring possible structural modifications of a previously identified xanthone scaffold. Among them, highly potent compounds, with inhibitory activity in the low nanomolar range, were found. In particular, substitution of the heterocyclic oxygen atom in the xanthone core by a sulfur atom and/or increase in structure flexibility seemed to be favorable for the interaction with the enzyme.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy. silvia.gobbi@unibo.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Christina
authors.initials: C
authors.lastname: Zimmer
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008968:Molecular Conformation; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013892:Thioxanthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D007093:Imidazoles; D013892:Thioxanthenes; D044004:Xanthones; D013254:Steroid 17-alpha-Hydroxylase