Selective inhibition of aromatase by a dihydroisocoumarin from Xyris pterygoblephara

J Nat Prod. 2008 Jun;71(6):1082-4. doi: 10.1021/np800098f. Epub 2008 May 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / isolation & purification*
  • Aromatase Inhibitors / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Isocoumarins / chemistry
  • Isocoumarins / isolation & purification*
  • Isocoumarins / pharmacology*
  • Magnoliopsida / chemistry*
  • Plants, Medicinal / chemistry*

Substances

  • (3R,4R)-(-)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1 H-isochromen-4-yl acetate
  • Antineoplastic Agents, Phytogenic
  • Aromatase Inhibitors
  • Isocoumarins