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 (IC₅₀ = 2.5 μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC₅₀ = 6.5–36.2 μM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server as a novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.

二十五个新颖烯醇酮/ 2-氰基丙烯缀合物（6 - 30）被设计和制备，以开发新的抗癌药物与双NF-κB的抑制和抗增殖活性的目的。化合物22和27 – 30在荧光素酶测定中显示出对TNF-α诱导的NF-κB活化的抑制作用，这已通过Western印迹证实。其中，化合物30显示出有效的NF-κB抑制活性（IC ₅₀  = 2.5μM），并且对MCF-7，A549，H157和HL-60细胞系具有抗增殖作用（IC ₅₀ = 6.5–36.2μM）。本研究表明，孕烯醇酮/ 2-氰基丙烯酰基共轭物I可以作为开发癌症化疗中NF-κB抑制剂和抗增殖剂的新型支架。