Endringer Denise C, Guimarães Keller G, Kondratyuk Tamara P, Pezzuto John M, Braga Fernão C
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, Brazil.
J Nat Prod. 2008 Jun;71(6):1082-4. doi: 10.1021/np800098f. Epub 2008 May 8.
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.
芳香化酶是乳腺癌化学预防中一个已确立的靶点。从翼萼黄眼草地上部分分离得到的二氢异香豆素(3R,4R)-(-)-6-甲氧基-1-氧代-3-戊基-3,4-二氢-1H-异色烯-4-基乙酸酯(1)(IC50 = 1.6±0.1μM)具有芳香化酶抑制活性。通过细胞色素P450酶抑制试验评估了化合物1的特异性。CYP1A1受到适度抑制(IC50 = 38.0±2.0μM),而CYP2C8和CYP3A4酶未受影响。二氢异香豆素1对MCF-7(IC50 = 66.9±2.3μM)和LNCaP(IC50 = 57.5±2.0μM)细胞显示出较弱的抗增殖活性,对培养中的LU-1和HepG2细胞无活性。这些结果证明了二氢异香豆素1作为选择性芳香化酶抑制剂的潜力。