title: Selective inhibition of aromatase by a dihydroisocoumarin from Xyris pterygoblephara.
abstract: Aromatase is a well-established target for the chemoprevention of breast cancer. The dihydroisocoumarin (3 R,4 R)-(-)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1 H-isochromen-4-yl acetate (1) (IC 50 = 1.6 +/- 0.1 microM), isolated from aerial parts of Xyris pterygoblephara, showed aromatase inhibitory activity. The specificity of 1 was evaluated by inhibition assays with cytochrome P450 enzymes. CYP1A1 was inhibited modestly (IC 50 = 38.0 +/- 2.0 microM), while CYP2C8 and CYP3A4 enzymes were not affected. Dihydroisocoumarin 1 showed weak antiproliferative activity against MCF-7 (IC 50 = 66.9 +/- 2.3 microM) and LNCaP (IC 50 = 57.5 +/- 2.0 microM) cells and was inactive against LU-1 and HepG2 cells in culture. These results demonstrate the potential of dihydroisocoumarin 1 to serve as a selective aromatase inhibitor.
authors.affiliation: Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, Brazil.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Endringer
authors.forename: Keller G
authors.initials: KG
authors.lastname: Guimarães
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Fernão C
authors.initials: FC
authors.lastname: Braga
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D049934:Isocoumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: C531290:(3R,4R)-(-)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1 H-isochromen-4-yl acetate; D000972:Antineoplastic Agents, Phytogenic; D047072:Aromatase Inhibitors; D049934:Isocoumarins