Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam.
College of Pharmacy, Chungbuk National University, 194-31, Osongsaengmyung-1, Heungdeok, Cheongju, Chungbuk, 28160, Republic of Korea.
Sci Rep. 2022 Feb 21;12(1):2886. doi: 10.1038/s41598-022-06887-0.
In our search for novel small molecules activating procaspase-3, we have designed and synthesized two series of novel (E)-N'-arylidene-2-(2-oxoindolin-1-yl)acetohydrazides (4) and (Z)-2-(5-substituted-2-oxoindolin-1-yl)-N'-(2-oxoindolin-3-ylidene)acetohydrazides (5). Cytotoxic evaluation revealed that the compounds showed notable cytotoxicity toward three human cancer cell lines: colon cancer SW620, prostate cancer PC-3, and lung cancer NCI-H23. Especially, six compounds, including 4f-h and 4n-p, exhibited cytotoxicity equal or superior to positive control PAC-1, the first procaspase-3 activating compound. The most potent compound 4o was three- to five-fold more cytotoxic than PAC-1 in three cancer cell lines tested. Analysis of compounds effects on cell cycle and apoptosis demonstrated that the representative compounds 4f, 4h, 4n, 4o and 4p (especially 4o) accumulated U937 cells in S phase and substantially induced late cellular apoptosis. The results show that compound 4o would serve as a template for further design and development of novel anticancer agents.
在寻找新型小分子激活 procaspase-3 的过程中，我们设计并合成了两个系列的新型(E)-N'-芳基亚甲基-2-(2-氧代吲哚啉-1-基)乙酰腙（4）和(Z)-2-(5-取代-2-氧代吲哚啉-1-基)-N'-(2-氧代吲哚啉-3-亚基)乙酰腙（5）。细胞毒性评估显示，这些化合物对三种人类癌细胞系：结肠癌 SW620、前列腺癌 PC-3 和肺癌 NCI-H23 表现出显著的细胞毒性。特别是 6 种化合物，包括 4f-h 和 4n-p，表现出与阳性对照 PAC-1（第一个激活 procaspase-3 的化合物）相当或更好的细胞毒性。在测试的三种癌细胞系中，最有效的化合物 4o 的细胞毒性比 PAC-1 高三到五倍。对化合物对细胞周期和凋亡的影响分析表明，代表性化合物 4f、4h、4n、4o 和 4p（尤其是 4o）使 U937 细胞在 S 期积累，并显著诱导晚期细胞凋亡。结果表明，化合物 4o 将作为进一步设计和开发新型抗癌药物的模板。
