An efficient synthesis of the Alpinia officinarum-derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone (1) and an α,β-unsaturated ketone (2) was developed starting from commercially available eugenol. Among these, compound 2 showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells. Besides reducing clonogenic cell survival, compound 2 dose-dependently increased the sub G1 cell population and arrested the G2-phase of the cell cycle, as revealed by flow cytometry. Mechanistically, compound 2 acts as an intracellular pro-oxidant by generating copious amounts of reactive oxygen species. Compound 2 also induced both loss of mitochondrial membrane potential (MMP) as well as lysosomal membrane permeabilization (LMP) in the MCF-7 cells. The impaired mitochondrial and lysosomal functions due to reactive oxygen species (ROS)-generation by compound 2 may contribute to its apoptotic property.

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山姜生物活性二芳基庚烷类化合物的合成及其对乳腺癌细胞抗癌特性的作用机制

从市售丁香酚开始，开发了一种有效合成山姜衍生的二芳基庚烷类化合物，即 β-羟基酮 ( 1 ) 和 α,β-不饱和酮 ( 2 ) 的对映异构体。其中，化合物2对人乳腺癌MCF-7细胞显示出优异的抗增殖作用。正如流式细胞术所揭示的那样，除了降低克隆形成细胞的存活率外，化合物2剂量依赖性地增加了亚 G1 细胞群并阻止了细胞周期的 G2 期。从机制上讲，化合物2通过产生大量活性氧而起到细胞内促氧化剂的作用。化合物2还诱导 MCF-7 细胞中线粒体膜电位 (MMP) 和溶酶体膜透化 (LMP) 的丧失。由于化合物2产生活性氧 (ROS) 导致的线粒体和溶酶体功能受损可能有助于其凋亡特性。