Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India, 400085.
Homi Bhabha National Institute, Anushaktinagar, Mumbai, India, 400094.
J Nat Prod. 2021 Feb 26;84(2):352-363. doi: 10.1021/acs.jnatprod.0c01012. Epub 2021 Feb 15.
An efficient synthesis of the -derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone () and an α,β-unsaturated ketone () was developed starting from commercially available eugenol. Among these, compound showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells. Besides reducing clonogenic cell survival, compound dose-dependently increased the sub G1 cell population and arrested the G2-phase of the cell cycle, as revealed by flow cytometry. Mechanistically, compound acts as an intracellular pro-oxidant by generating copious amounts of reactive oxygen species. Compound 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 may contribute to its apoptotic property.
从商业上可获得的丁香酚出发，开发了一种高效合成 -衍生的二芳基庚烷类化合物，即对映体的β-羟基酮（）和α，β-不饱和酮（）。在这些化合物中，化合物对人乳腺癌 MCF-7 细胞显示出优越的抗增殖作用。除了降低集落形成细胞的存活率外，化合物还通过流式细胞术显示剂量依赖性地增加亚 G1 细胞群并使细胞周期停滞在 G2 期。从机制上讲，化合物通过产生大量的活性氧作为细胞内的促氧化剂。化合物还诱导 MCF-7 细胞中的线粒体膜电位（MMP）丧失以及溶酶体膜通透性（LMP）。由于化合物产生的活性氧（ROS），受损的线粒体和溶酶体功能可能有助于其凋亡特性。
