Selective inhibition of aromatase by a dihydroisocoumarin from Xyris pterygoblephara.
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.
Endringer
Denise C
DC
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, Brazil.
Guimarães
Keller G
KG
Kondratyuk
Tamara P
TP
Pezzuto
John M
JM
Braga
Fernão C
FC
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*
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