In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC₅₀ = 1.61 μM; 21, IC₅₀ = 3.05 μM; and 27, IC₅₀ = 3.34 μM) showed aromatase inhibitory activity with half maximal inhibitory concentration (IC₅₀) values in the low micromolar concentrations. With regard to the QR1 induction activity, 11 exhibited the highest QR1 induction ratio (IR) with a low concentration to double activity (CD) value (IR = 8.34, CD = 2.75 μM), while 7 showed the most potent CD value of 1.12 μM. A dual acting compound 24 showed aromatase inhibition (IC₅₀ = 9.00 μM) as well as QR1 induction (CD = 5.76 μM) activities. Computational docking studies using CDOCKER (Discovery Studio 3.5) provided insight in regard to the potential binding modes of 2-arylindoles within the aromatase active site. Predominantly, the 2-arylindoles preferred binding with the 2-aryl group toward a small hydrophobic pocket within the active site. The C-5 electron withdrawing group on indole was predicted to have an important role and formed a hydrogen bond with Ser478 (OH). Alternatively, meta-pyridyl analogs may orient with the pyridyl 3′-nitrogen coordinating with the heme group.

在我们不断发现抗癌和化学预防药物的过程中，合成了一系列 2-芳基吲哚衍生物，并针对芳香酶和醌还原酶 1 (QR1) 进行了评估。生物学评价显示，几种化合物（例如， 2d ，IC ₅₀ = 1.61 μM； 21 ，IC ₅₀ = 3.05 μM； 27 ，IC ₅₀ = 3.34 μM）显示出芳香酶抑制活性，最大抑制浓度（IC ₅₀ ）值的一半。低微摩尔浓度。就 QR1 诱导活性而言， 11 种表现出最高的 QR1 诱导率 (IR)，但浓度双倍活性 (CD) 值较低（IR = 8.34，CD = 2.75 μM），而7 种表现出最强的 CD 值，为 1.12微米。双重作用化合物24显示出芳香酶抑制 (IC ₅₀ = 9.00 μM) 以及 QR1 诱导 (CD = 5.76 μM) 活性。使用 CDOCKER (Discovery Studio 3.5) 进行的计算对接研究提供了有关芳香酶活性位点内 2-芳基吲哚的潜在结合模式的见解。主要是，2-芳基吲哚优选与2-芳基基团朝向活性位点内的小疏水袋结合。吲哚上的C-5吸电子基团被预测具有重要作用并与Ser478(OH)形成氢键。或者，间吡啶基类似物可以与与血红素基团配位的吡啶基3'-氮取向。