期刊
PHARMACEUTICS
卷 13, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13060788
关键词
phospholipids metabolism; choline kinase; bispyridinium compounds; bisquinolinium compounds; QSAR; anticancer drugs; rheumatoid arthritis; parasites; pathogenic bacteria; inflammatory disease
资金
- CSIC [PIE202020E041]
- NIFA through the Agricultural Research Program at North Carolina Agricultural and Technical State University (Evans-Allen Program) [NC.X-291-5-15-170-1]
Choline kinase plays a crucial role in human tumors and specific compounds targeting it have been identified as potential anticancer agents. Some of these compounds have shown selective anticancer activity and have progressed to clinical trials. Additionally, ChoK alpha inhibitors are proposed as a novel therapeutic approach against various diseases.
Choline kinase (ChoK) is a cytosolic enzyme that catalyzes the phosphorylation of choline to form phosphorylcholine (PCho) in the presence of ATP and magnesium. ChoK is required for the synthesis of key membrane phospholipids and is involved in malignant transformation in a large variety of human tumours. Active compounds against ChoK have been identified and proposed as antitumor agents. The ChoK inhibitory and antiproliferative activities of symmetrical bispyridinium and bisquinolinium compounds have been defined using quantitative structure-activity relationships (QSARs) and structural parameters. The design strategy followed in the development of the most active molecules is presented. The selective anticancer activity of these structures is also described. One promising anticancer compound has even entered clinical trials. Recently, ChoK alpha inhibitors have also been proposed as a novel therapeutic approach against parasites, rheumatoid arthritis, inflammatory processes, and pathogenic bacteria. The evidence for ChoK alpha as a novel drug target for approaches in precision medicine is discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据