Boesenbergia pandurata as Anti-breast Cancer: Molecular Docking and ADMET Study

<em>Boesenbergia pandurata</em> or fingerroot is known to have various pharmacological activities, including anticancer. Extracts from these plants are known to inhibit the growth of cancer cells, including breast cancer. Anti-breast cancer activity is significantly influenced by the inhibition of two receptors: ER-α and HER2. However, it is unknown which metabolites of <em>B. pandurata</em> play the most crucial role in their anticancer activity. This study aimed to determine the metabolites of <em>B. pandurata</em> with the best potential as ER-α and HER2 inhibitors. The method used was molecular docking of several <em>B. pandurata</em> metabolites against ER-α and HER2 receptors, followed by an ADMET study of several metabolites with the best docking results. The docking results showed eight metabolites with the best docking results for the two receptors based on the docking score and ligand-receptor interactions. Of these eight compounds, compounds <strong>11</strong> ((2S)-7,8-dihydro-5-hydroxy-2-methyl-2-(4''-methyl-3''-pentenyl)-8-phenyl-2H,6H-benzo(1,2-b-5,4-b')dipyran-6-one) and <strong>34</strong> (geranyl-2,4-dihydroxy-6-phenethylbenzoate) showed the potential to inhibit both receptors. Both ADMET profiles also show mixed results but still allow for further development. In conclusion, the metabolites of <em>B. pandurata</em> especially compounds <strong>11</strong> and <strong>34</strong>, can be developed as anti-breast cancer through the inhibition of ER-α and HER2.手指姜（Boesenbergia pandurata）俗称fingerroot，被证实具备多种药理活性，其中包括抗肿瘤活性。该植物提取物可抑制包括乳腺癌在内的多种癌细胞增殖，其抗乳腺癌活性主要通过调控两种受体的抑制作用实现：雌激素受体α（ER-α）与人表皮生长因子受体2（HER2）。然而目前尚不清楚该植物的哪些代谢产物在其抗肿瘤活性中发挥最为关键的作用。本研究旨在筛选出在ER-α和HER2抑制方面潜力最优的手指姜代谢产物。研究采用的方法为：先对多种手指姜代谢产物开展针对ER-α和HER2受体的分子对接（molecular docking）实验，随后对对接结果最优的数种代谢产物进行ADMET（吸收-分布-代谢-排泄-毒性）分析。分子对接结果显示，基于对接得分与配体-受体相互作用，共有8种代谢产物对这两种受体的对接效果最优。在这8种化合物中，化合物11（(2S)-7,8-二氢-5-羟基-2-甲基-2-(4""-methyl-3""-pentenyl)-8-phenyl-2H,6H-benzo(1,2-b:5,4-b')dipyran-6-one）与化合物34（geranyl-2,4-dihydroxy-6-phenethylbenzoate）显示出同时抑制两种受体的潜力。二者的ADMET特性均呈现出混合性结果，但仍具备进一步开发的价值。综上，手指姜的代谢产物，尤其是化合物11与34，可通过抑制ER-α和HER2靶点开发为抗乳腺癌候选药物。