With the help of the establishment of novel reaction methodology, a series of N-Aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-one conjugates were designed and synthesized in 2–4 steps, and subsequent anticancer activity of these compounds was evaluated. Preliminary results showed that these compounds have moderate to potent activities against human acute leukemia cells K562, human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 2d and 2k were the most potent against K562 cell line with IC₅₀ values of 0.07 and 0.52 µM, respectively, and the toxicity of 2d to the normal of hepatocytes (LO2) cell line was low (the survival rate 81 %). Flow cytometry analysis showed that 2d arrested K562 cells in the G2/M phase potently, even much better than Combretastatin A4 (CA4). In addition, the results demonstrated the involvement of the caspase-dependent or independent pathways of apoptosis, evidenced by the upregulation of FADD, pro-caspase 3, cleaved-caspase 3, HTRA2/Omi, SMAC/Diablo and the ratio of Bax/Bcl-2.The biological effects founding of 2d in this work point to prospective uses against acute leukemia.

借助新反应方法的建立，设计并合成了一系列N -Aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2 H -pyrrol-2-one 偶联物。 2-4 个步骤，然后评估这些化合物的后续抗癌活性。初步结果表明，这些化合物对人急性白血病细胞 K562、人肺癌 A549、人乳腺癌 MDA-MB-231 和人宫颈癌 HeLa 癌细胞系具有中度至强效的活性。其中，化合物2d和2k对K562细胞系最有效，IC ₅₀值分别为0.07和0.52 µM，毒性为2d对正常肝细胞（LO2）细胞系低（存活率81%）。流式细胞仪分析显示，2d有效地将 K562 细胞阻滞在 G2/M 期，甚至比 Combretastatin A4 (CA4) 好得多。此外，结果表明参与了半胱天冬酶依赖性或独立的细胞凋亡途径，这可以通过 FADD、半胱天冬酶原 3、切割半胱天冬酶 3、HTRA2/Omi、SMAC/Diablo 和 Bax/Bcl 比值的上调来证明。 -2.这项工作中2d的生物学效应指向了对急性白血病的潜在用途。