Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Bioorg Chem. 2020 Mar;96:103609. doi: 10.1016/j.bioorg.2020.103609. Epub 2020 Jan 21.
Hexokinase 2 (HK2) is over-expressed in most of human cancers and has been proved to be a promising target for cancer therapy. In this study, based on the structure of HK2, we screened over 6 millions of compounds to obtain the lead. A total of 26 (E)-N'-(2,3,4-trihydroxybenzylidene) arylhydrazide derivatives were then designed, synthesized, and evaluated for their HK2 enzyme activity and IC values against two cancer cell lines. Most of the 26 target compounds showed excellently in vitro activity. Among them, compound 3j showed the strongest inhibitory effects on HK2 enzyme activity with an IC of 0.53 ± 0.13 μM and exhibited the most potent growth inhibition against SW480 cells with an IC of 7.13 ± 1.12 μM, which deserves further studies.
己糖激酶 2（HK2）在大多数人类癌症中过表达，已被证明是癌症治疗的有前途的靶点。在这项研究中，我们基于 HK2 的结构，筛选了超过 600 万种化合物以获得先导化合物。然后设计、合成了总共 26 种（E）-N'-(2,3,4-三羟基苯亚甲基)芳腙衍生物，并评估了它们对 HK2 酶活性和对两种癌细胞系的 IC 值。26 个目标化合物中的大多数在体外表现出优异的活性。其中，化合物 3j 对 HK2 酶活性的抑制作用最强，IC 为 0.53±0.13μM，对 SW480 细胞的生长抑制作用最强，IC 为 7.13±1.12μM，值得进一步研究。
