Faculty of Environment and Life, Beijing University of Technology, Beijing, China.
Beijing Tide Pharmaceutical Co., Ltd, Beijing, China.
Chem Biol Drug Des. 2023 Mar;101(3):568-580. doi: 10.1111/cbdd.14145. Epub 2022 Sep 21.
In our research on novel anticancer agents, a series of N -hydrazone purine derivatives were designed and synthesized by analysis of a pharmacophore model for ATP-competitive inhibitors. The activities screening results showed that N -hydrazone purine derivatives 21 and 26 not only showed potential antiproliferative activity against the A549 and MCF-7 cell lines comparable to Vandetanib as a positive control but also had moderate antiplatelet aggregation activity. In order to investigate the possible targets, a molecular docking study was carried out on the fourteen kinases associated with anticancer and antiplatelet aggregation activities. The results indicated that compounds 21 and 26 had the potential activity to target VEGFR-2, PI3Kα, EGFR, and HER2 kinases. The inhibition of the kinases assay showed that compound 26 could target VEGFR-2, PI3Kα, and EGFR (IC = 0.822, 3.040 and 6.625 μM). All results indicated that compound 26 will be an encouraging framework as potential new multi-target anticancer agent with potential antiplatelet aggregation activity.
在我们对新型抗癌药物的研究中，通过对 ATP 竞争性抑制剂的药效团模型分析，设计并合成了一系列 N -腙嘌呤衍生物。活性筛选结果表明，N -腙嘌呤衍生物 21 和 26 不仅对 A549 和 MCF-7 细胞系表现出与阳性对照凡德他尼相当的潜在抗增殖活性，而且还具有中等的抗血小板聚集活性。为了研究可能的靶点，对与抗癌和抗血小板聚集活性相关的 14 种激酶进行了分子对接研究。结果表明，化合物 21 和 26 具有靶向 VEGFR-2、PI3Kα、EGFR 和 HER2 激酶的潜在活性。激酶抑制试验表明，化合物 26 可靶向 VEGFR-2、PI3Kα 和 EGFR（IC 50 = 0.822、3.040 和 6.625 μM）。所有结果表明，化合物 26 将成为一种有希望的多靶抗癌药物的新骨架，具有潜在的抗血小板聚集活性。
