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
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.
引用
收藏
页数:9
相关论文
共 50 条
[41]   New Human Monoamine Oxidase A Inhibitors with Potential Anti-Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity [J].
Evranos-Aksoz, Begum ;
Ucar, Gulberk ;
Tas, Sadik Taskin ;
Aksoz, Erkan ;
Yelekci, Kemal ;
Erikci, Acelya ;
Sara, Yildirim ;
Iskit, Alper Bektas .
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2017, 20 (06) :461-473
[42]   Identification of novel and potent dual-targeting HDAC1/SPOP inhibitors using structure-based virtual screening, molecular dynamics simulation and evaluation of in vitro and in vivo antitumor activity [J].
Yang, Yingxue ;
Chen, Shutong ;
Wang, Qinghua ;
Niu, Miao-Miao ;
Qu, Yuanqian ;
Zhou, Yang .
FRONTIERS IN PHARMACOLOGY, 2023, 14
[43]   Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation [J].
Zhang, Hui ;
Shen, Chen ;
Zhang, Hong-Rui ;
Qi, Hua-Zhao ;
Hu, Mei-Ling ;
Luo, Qing-Qing .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (15)
[44]   Virtual screening based on pharmacophoric features of known calpain inhibitors to identify potent inhibitors of calpain [J].
Muralidharan, Arumugam Ramachandran ;
Selvaraj, Chandrabose ;
Singh, Sanjeev Kumar ;
Jesudasan, C. A. Nelson ;
Geraldine, Pitchairaj ;
Thomas, Philip A. .
MEDICINAL CHEMISTRY RESEARCH, 2014, 23 (05) :2445-2455
[45]   Virtual screening based on pharmacophoric features of known calpain inhibitors to identify potent inhibitors of calpain [J].
Arumugam Ramachandran Muralidharan ;
Chandrabose Selvaraj ;
Sanjeev Kumar Singh ;
C. A. Nelson Jesudasan ;
Pitchairaj Geraldine ;
Philip A. Thomas .
Medicinal Chemistry Research, 2014, 23 :2445-2455
[46]   Identification of Pim-1 Kinase Inhibitors by Pharmacophore Model, Molecular Docking-based Virtual Screening, and Biological Evaluation [J].
Huang, Jing ;
Yuan, Ye ;
Zhu, Xiaoxiao ;
Li, Guodong ;
Xu, Ya ;
Chen, Wenlin ;
Zhu, Ying .
CURRENT COMPUTER-AIDED DRUG DESIGN, 2022, 18 (03) :240-246
[47]   Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity [J].
Zhu, Kongkai ;
Shao, Jingwei ;
Tao, Hongrui ;
Yan, Xue ;
Luo, Cheng ;
Zhang, Hua ;
Duan, Wenhu .
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2019, 33 (08) :775-785
[48]   Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus [J].
V. Karthick ;
N. Nagasundaram ;
C. George Priya Doss ;
Chiranjib Chakraborty ;
R. Siva ;
Aiping Lu ;
Ge Zhang ;
Hailong Zhu .
Infectious Diseases of Poverty, 5
[49]   Structure-based virtual screening and biological evaluation of novel small-molecule BTK inhibitors [J].
Lin, Tony Eight ;
Sung, Li-Chin ;
Chao, Min-Wu ;
Li, Min ;
Zheng, Jia-Huei ;
Sung, Tzu-Ying ;
Hsieh, Jui-Hua ;
Yang, Chia-Ron ;
Lee, Hsueh-Yun ;
Cho, Er-Chieh ;
Hsu, Kai-Cheng .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2022, 37 (01) :226-235
[50]   Discovery, Biological Evaluation and Binding Mode Investigation of Novel Butyrylcholinesterase Inhibitors Through Hybrid Virtual Screening [J].
Li, Lizi ;
Zhao, Puchen ;
Yang, Can ;
Yin, Qin ;
Wang, Na ;
Liu, Yan ;
Li, Yanfang .
MOLECULES, 2025, 30 (10)