School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
Steroids. 2019 Dec;152:108499. doi: 10.1016/j.steroids.2019.108499. Epub 2019 Sep 16.
A series of new cinnamic acid-pregenolone hybrids (5a-5o) was designed, synthesized and evaluated for their in vitro antiproliferative activity. Some of them showed potential antiproliferative activity and selectivity towards a panel of cancer cell lines, including A549, H157, HepG2, MCF-7, and HL-60. Among these analogs, compound 5f showed the most promising activity with IC values ranging from 3.2 to 6.8 μM, and it was taken as a model compound in the following antiproliferative mechanism study. In Hoechst 33258 staining assay, 5f-treated A549 cells displayed significant apoptosis characteristics. Flow cytometry analysis revealed that 5f showed the antiproliferative activity against A549 via G1 cell cycle arrest and inducing apoptosis. Western blotting analysis demonstrated that 5f enhanced apoptosis of A549 cells by down-regulating Bcl-2 and up-regulating Bax protein expression. The present study highlighted this series of cinnamic acid-pregenolone hybrids as a new antiproliferative lead prototype.
设计、合成了一系列新的肉桂酸孕烯醇酮杂合体（5a-5o），并评估了它们对体外增殖活性的抑制作用。其中一些化合物对一组癌细胞系（包括 A549、H157、HepG2、MCF-7 和 HL-60）显示出潜在的增殖活性和选择性。在这些类似物中，化合物 5f 表现出最有前途的活性，IC 值范围为 3.2 至 6.8µM，它被选为后续增殖抑制机制研究的模型化合物。在 Hoechst 33258 染色试验中，5f 处理的 A549 细胞显示出明显的凋亡特征。流式细胞术分析表明，5f 通过 G1 细胞周期阻滞和诱导细胞凋亡来抑制 A549 的增殖活性。Western blot 分析表明，5f 通过下调 Bcl-2 和上调 Bax 蛋白表达来增强 A549 细胞的凋亡。本研究强调了这一系列肉桂酸孕烯醇酮杂合体作为一种新的增殖抑制先导原型。
