Novel highly potent and selective nonsteroidal aromatase inhibitors: synthesis, biological evaluation and structure-activity relationships investigation.
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.
Gobbi
Silvia
S
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy. silvia.gobbi@unibo.it
Zimmer
Christina
C
Belluti
Federica
F
Rampa
Angela
A
Hartmann
Rolf W
RW
Recanatini
Maurizio
M
Bisi
Alessandra
A
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
D047072:Aromatase Inhibitors; D007093:Imidazoles; D013892:Thioxanthenes; D044004:Xanthones; D013254:Steroid 17-alpha-Hydroxylase