具有双重NF-κB抑制和抗增殖活性的孕烯醇酮/2-氰基丙烯酰基缀合物的设计与合成
Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities.
作者信息
Song Jia-Li, Zhang Juan, Liu Chang-Liang, Liu Chao, Zhu Kong-Kai, Yang Fei-Fei, Liu Xi-Gong, Figueiró Longo João Paulo, Alexandre Muehlmann Luis, Azevedo Ricardo Bentes, Zhang Yu-Ying, Guo Yue-Wei, Jiang Cheng-Shi, Zhang Hua
机构信息
School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
Faculty of Ceilandia, University of Brasilia, Brasilia 72220275, Brazil; Institute of Biological Sciences, University of Brasília, Brasília 70910900, Brazil.
出版信息
Bioorg Med Chem Lett. 2017 Oct 15;27(20):4682-4686. doi: 10.1016/j.bmcl.2017.09.013. Epub 2017 Sep 8.
Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC=2.5μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC=6.5-36.2μM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.
设计并制备了25种新型孕烯醇酮/2-氰基丙烯酰缀合物（6-30），目的是开发具有双重NF-κB抑制和抗增殖活性的新型抗癌药物。化合物22以及27-30在荧光素酶测定中显示出对TNF-α诱导的NF-κB激活的抑制作用，这通过蛋白质免疫印迹得到证实。其中，化合物30显示出强大的NF-κB抑制活性（IC = 2.5μM）以及对MCF-7、A549、H157和HL-60细胞系的抗增殖活性（IC = 6.5-36.2μM）。本研究表明，孕烯醇酮/2-氰基丙烯酰缀合物I可作为癌症化疗中开发NF-κB抑制剂和抗增殖剂的新型骨架。
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