相关实验视频

Updated: Jan 16, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

发现和分子对接研究含有的纳夫铁衍生物作为具有抗癌潜力的强效HIV1NNRTIs

Apisara Baicharoen¹, Pongsit Vijitphan¹, Suwicha Patnin¹

¹Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, Bangkok, 10210, Thailand.

Scientific reports

|September 30, 2025

概括

新型纳夫提里丁衍生物显示出强大的HIV-1RT抑制和有前途的抗癌活性. 这些通过分子杂交设计的化合物为开发抗HIV和抗癌药物提供了新的途径.

科学领域:

药用化学医学化学
有机合成有机合成
药物发现药物发现药物发现

背景情况:

人类免疫缺陷病毒 (HIV) 感染仍然是一个全球性的健康挑战.
开发针对HIV-1逆转录酶 (RT) 的新型抑制剂对于有效的抗逆转录病毒疗法至关重要.
非核类逆转录酶抑制剂 (NNRTIs) 是一种关键类型的抗逆转录病毒药物.

研究的目的:

为了合成和评估新型的2,4-非替代-1,6-和1,7-纳二衍生物作为潜在的HIV-1RT抑制剂.
为了探索这些合成的纳二衍生物的潜在抗癌特性.
研究最强效化合物的结构-活性关系和结合机制.

主要方法:

通过尼古丁酸相似物,核爱置换和布丘瓦尔德-哈特维格反应合成14种新型的2,4-非替代-1,6-和1,7-纳弗提里丁衍生物.
在体外评估HIV-1RT抑制活性,对癌细胞系和正常细胞系的细胞毒性.
分子对接和分子动力学模拟以阐明HIV-1 RT活性部位内的结合模式.
使用利宾斯基的五项规则进行药理动力学分析.

主要成果:

化合物16a,16b和19a表现出显著的HIV-1RT抑制,IC50值分别为0.222,0.218和0.175μM,表现优于内维拉平,与里尔皮维林和埃法维伦兹相当.
分子对接和动力学模拟证实了HIV-1RT口袋中对强效化合物的有利结合相互作用.
几种纳胺衍生物对各种癌细胞系表现出显著的细胞毒性,其中化合物17a对MOLT-3,HeLa和HL-60细胞表现出显著的活性.
化合物16a,16b和19a对正常的胚胎肺细胞 (MRC-5) 没有毒性,所有化合物都遵守了利宾斯基的五项规则.

结论:

合成的2,4-非替代-1,6-和1,7-纳二衍生物代表了HIV-1RT抑制的一类有前途的化合物.
这些纳夫胺衍生物还具有显著的抗癌潜力,这表明它们具有双重的治疗应用.
对这些化合物的进一步研究可能会导致对艾滋病毒/艾滋病和癌症治疗的新疗法的开发.

关键词:

这是一种抗癌药物.细胞毒性细胞毒性艾滋病病毒-1 艾滋病病毒-1 分子对接是分子对接.纳甲基氨酸 (NAPHTHYRIDINE) 是一种氨酸.奎诺林 (quinoline) 是一种氨酸.

更多相关视频

Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors

Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors

Published on: January 19, 2015

Peptide-based Identification of Functional Motifs and their Binding Partners

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

相关概念视频

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...