title: Combining computational and biochemical studies for a rationale on the anti-aromatase activity of natural polyphenols.
abstract: Aromatase, an enzyme of the cytochrome P450 family, is a very important pharmacological target, particularly for the treatment of breast cancer. The anti-aromatase activity of a set of natural polyphenolic compounds was evaluated in vitro. Strong aromatase inhibitors including flavones, flavanones, resveratrol, and oleuropein, with activities comparable to that of the reference anti-aromatase drug aminoglutethimide, were identified. Through the application of molecular modeling techniques based on grid-independent descriptors and molecular interaction fields, the major physicochemical features associated with inhibitory activity were disclosed, and a putative virtual active site of aromatase was proposed. Docking of the inhibitors into a 3D homology model structure of the enzyme defined a common binding mode for the small molecules under investigation. The good correlation between computational and biological results provides the first rationalization of the anti-aromatase activity of polyphenolic compounds. Moreover, the information generated in this approach should be further exploited for the design of new aromatase inhibitors.
authors.affiliation: Centro de Estudos Farmacêuticos, Lab. Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal.
authors.forename: Marco A C
authors.initials: MA
authors.lastname: Neves
authors.forename: Teresa C P
authors.initials: TC
authors.lastname: Dinis
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Sá e Melo
mesh_terms: D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008861:Microsomes / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects; D059808:Polyphenols; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols