Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II

被引:3
作者
Liu, Ruijuan [1 ]
Liu, Xuewei [2 ]
机构
[1] Northwest Normal Univ, Coll Phys Educ, Lanzhou 730070, Peoples R China
[2] Jiangsu Food & Pharmaceut Sci Coll, Dept Pharm, Huaian 223003, Peoples R China
来源
MOLECULES | 2022年 / 27卷 / 21期
关键词
Hexokinase-II; molecular docking; inhibitor; virtual screen; small molecule; GLUCOSE-METABOLISM; CANCER; METFORMIN; GROWTH; TUMORS;
D O I
10.3390/molecules27217555
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy.
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收藏
页数:9
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