通过分子对接和生物学评价洞察氯化两面针碱的NEk2抑制谱。

Insights into an NEk2 inhibitory profile of nitidine chloride by molecular docking and biological evaluation.

作者信息

Li Danni, Lu Jiahao, Zhang Qiying, Zhou Yuzhu, Li Long, Zhu Hua, Li Tong

机构信息

School of Chemistry and Chemical Engineering, Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Minzu University, No.158, Da Xue Xi street, Xixiangtang District, Nanning, 530006, Guangxi, China.

College of Pharmacy, Guangxi University for Chinese Medicine, No.13, Wu He street, Qingxiu District, Nanning, 530200, Guangxi, China.

出版信息

BMC Chem. 2022 Oct 9;16(1):75. doi: 10.1186/s13065-022-00870-6.

DOI:10.1186/s13065-022-00870-6

PMID:36210464

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9549606/

Abstract

Deregulation of NEK2(NIMA-related serine/threonine 2) confers chemotherapeutic resistance to apoptosis and is closely correlated with poor prognosis in hepatocellular carcinoma (HCC). Here, we find that nanoparticles are prepared through hemisynthesis from natural nitidine chloride (NC) with enhanced antitumor activity. Nitidine chloride nanoparticle (TPGS-FA/NC) treatment show good therapy effect in Li-7 hepatocellular carcinoma cells. Additionally, molecular docking technologies are aimed at NEK2 protein (PDB ID: 6SGD) to analyze the detailed binding interactions with the potent target. NC participates in interactions with Asp159 residue. These studies advance the understanding of the modification of nitidine chloride substituent and provide useful drug design information for liver cancer treatment.

摘要

NEK2（与NIMA相关的丝氨酸/苏氨酸激酶2）的失调赋予了对凋亡的化疗抗性，并且与肝细胞癌（HCC）的不良预后密切相关。在此，我们发现通过从天然氯化两面针碱（NC）进行半合成制备的纳米颗粒具有增强的抗肿瘤活性。氯化两面针碱纳米颗粒（TPGS-FA/NC）处理在Li-7肝癌细胞中显示出良好的治疗效果。此外，分子对接技术针对NEK2蛋白（PDB ID：6SGD），以分析与有效靶点的详细结合相互作用。NC参与与Asp159残基的相互作用。这些研究推进了对氯化两面针碱取代基修饰的理解，并为肝癌治疗提供了有用的药物设计信息。