Background: Electrophilic compounds bearing Michael acceptors present great promise in anticancer drug discovery.

Methods: Drawing inspirations from cytotoxic Piper lactam alkaloids, twelve N-acylated butyro- and valerolactams were prepared and evaluated for antiproliferative and cytotoxic activities against the normal human umbilical vein endothelial cells (HUVEC), chronic human myeloid leukemia cells (K- 562), and Henrietta Lacks (HeLa) cells used as model cell lines. Molecular docking of bioactive derivatives was performed against tyrosine kinase.

Results: Results of the MTT assay showed the crotonylated (5) and nitro-containing cinnamoyl (8) butyrolactams, and, the crotonylated (10), trifluoromethylated (13), and chlorinated (14) cinnamoyl valerolactam derivatives as the most antiproliferative against human myeloid leukemia cells. The trifluoromethylated cinnamoyl valerolactam (13) displayed the best selectivity on K-562 cells. Molecular docking studies of 13 against tyrosine kinase provided evidence as tyrosine kinase inhibitor, having comparable binding energy and receptor interaction with imatinib.

Conclusion: The presence of electrophilic N-acrylic moieties contributes to the potential of a compound as inspiration to develop anti-leukemia drugs.

背景：带有迈克尔受体的亲电子化合物在抗癌药物发现中具有广阔的前景。

方法：从具有细胞毒性的Piper内酰胺生物碱中提取灵感，制备了12种N-酰化的丁酰和戊内酰胺，并评估了它们对正常人脐静脉内皮细胞（HUVEC），慢性人髓样白血病细胞（K-562）的抗增殖和细胞毒性活性，和Henrietta Lacks（HeLa）细胞用作模型细胞系。针对酪氨酸激酶进行生物活性衍生物的分子对接。

结果：MTT分析的结果表明，巴豆酰化（5）和含硝基的肉桂酰（8）丁内酰胺，以及巴豆酰化（10），三氟甲基化（13）和氯化（14）的肉桂酰戊内酰胺衍生物对人的抗增殖性最强髓样白血病细胞。三氟甲基化肉桂酰基戊内酰胺（13）在K-562细胞上显示出最佳选择性。13对酪氨酸激酶的分子对接研究提供了酪氨酸激酶抑制剂的证据，具有与伊马替尼相当的结合能和受体相互作用。

结论：亲电性N-丙烯酸部分的存在有助于该化合物作为开发抗白血病药物的灵感的潜力。