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对4-anilinoquinazoline EGFR 抑制剂的素诱导变化的洞察:一个计算光谱研究

Sallam Alagawani¹, Vladislav Vasilyev², Andrew H A Clayton³

¹Department of Chemistry and Biotechnology, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, Melbourne, VIC 3122, Australia.

Molecules (Basel, Switzerland)

|June 27, 2024

概括

在表皮生长因子受体 (EGFR) 抑制剂中的素替代影响电子特性和光谱特征,与药物的效力相关. 有效的抑制剂表现出更大的灵活性和明显的二极极时刻,这表明用于评估疗效的光学报告.

科学领域:

药用化学医学化学
计算化学的计算化学
生物化学生物化学

背景情况:

表皮生长因子受体 (EGFR) 是癌症治疗的关键标.
4-anilinoquinazoline衍生物是强大的EGFR抑制剂.
素替代影响EGFR抑制剂的功效,但机制尚不清楚.

研究的目的:

研究素替代 (H,F,Cl,Br,I) 对4-anilinoquinazoline EGFR 抑制剂的结构,特性和光谱的影响.
阐明素替代,分子特性和氨酸激酶抑制剂 (TKI) 功效之间的关系.

主要方法:

时间依赖密度函数理论 (TD-DFT) 具有B3LYP函数.
分析电子属性 (双极时刻,空间范围).
紫外线可见光谱分析和与实验功率 (IC50值) 的相关性.
形态分析和与晶体结构的比较.

主要成果:

素替代改变电子属性和二极矩,影响EGFR结合.
功效与较短的紫外线可见吸收波长 (蓝色转移) 相对应.
更强大的抑制剂 (TKI-Cl,TKI-Br) 显示出更大的灵活性和更高的双极时刻.
最佳药物构造可能不是全球最低能量结构.

结论:

素替代显著调节EGFR抑制剂的电子和光谱特性.
二极子时刻和光谱变化是TKI功能的可靠指标.
分子灵活性和特定的低型对象对于高药疗效至关重要.
光学报告提供了一种探测药物效能和形状动态的方法.

关键词:

吸收光谱法是一种吸收光谱法.皮肤上生长因子受体 (EGFR)时间依赖密度函数理论 (TD-DFT)氨酸激酶抑制剂 (TKI) 的使用紫外线可见 (UV-Vis) 的紫外线

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