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由计算分析支持的广泛治疗应用的Pyrido[2,3-d]pyrimidine支架的创新性氨基功能化

Hagar S El-Hema¹, Haitham E Shehata², Mohamed A Hawata²

¹Basic Science Department (Chemistry), Thebes Higher Institute for Engineering, Thebes Academy, Maadi 11434, Egypt.

Pharmaceuticals (Basel, Switzerland)

|October 29, 2025

概括

皮里多[2,3-d]皮里米丁衍生物显示出双重抗癌和抗菌潜力. 化合物1有效抑制EGFR突变和细菌生长,显示出作为多目标治疗剂的前景.

科学领域:

药用化学医学化学
药理学药理学是指药理学的学科.
计算化学的计算化学

背景情况:

化[2,3-d]胺-6-碳酸盐衍生物作为开发多目标治疗剂的多功能支架.
本研究探讨了新型氨基功能化衍生物的合成和双重抗癌和抗菌评估.

研究的目的:

合成和表征16种新型的pyrido[2,3-d]pyrimidine衍生物. 为了合成和表征16种新的pyrido[2,3-d]pyrimidine衍生物.
评估它们对人类癌细胞系 (HeLa,HepG-2,MCF-7) 的抗癌活性以及对正常细胞 (WI-38) 的选择性.
评估它们对野生型 (EGFR^WT) 和突变型 (EGFR^T790M) 表皮生长因子受体 (EGFR) 的抑制潜力.
为了研究它们对抗革兰氏阴性细菌的抗菌功效 (E. 大肠杆菌,P. coli,P. 飞 (英语:Aeruginosa) 是一种飞.
进行机理学研究,包括细胞周期,细胞亡和迁移分析.
进行in silico分析,包括ADMET分析,分子对接,分子动力学,DFT和抗病毒预测.

主要方法:

合成了16种氨基功能化的pyrido[2,3-d]pyrimidine衍生物.
在体外细胞毒性试验,EGFR抑制试验,细胞周期分析,细胞亡试验和细胞迁移试验.
使用最小抑制度 (MIC) 确定进行抗菌活性测试.
在 silico ADMET 预测,分子对接,分子动力学模拟和密度函数理论 (DFT) 计算.
在的抗病毒查针对选择的病毒标.

主要成果:

衍生物1,2,和7对癌细胞系表现出显著的细胞毒性 (IC₅₀ = 3.98-17.52 μM),对正常细胞具有良好的选择性.
化合物1显示出对EGFR^WT (IC₅₀ = 0.093μM) 和EGFR^T790M (IC₅₀ = 0.174μM) 的强烈抑制,诱导G0/G1细胞周期停止和细胞亡,并减少癌细胞迁移.
观察到适度的抗菌活性 (MIC = 50μg/mL).
在基分析预测了衍生品的有利的药物动力学特性,低CYP抑制,没有变异性,以及口服毒性III类.
分子动力学模拟证实了与EGFR标的稳定结合相互作用.
在的抗病毒评估表明,对包括HCV NS5A,SARS-CoV-2 Mpro和E. 大肠杆菌的DNA旋转酶.

结论:

化合物1具有显著的双重抗癌和抗菌活性,通过机械学和计算研究进行验证.
皮里多[2,3-d] 皮里米丁衍生物代表了癌症和传染病的多目标治疗支架的一个有前途的类别.
对化合物1进行进一步的研究对于其潜在的治疗应用是有必要的.

关键词:

在 DFT 方面,它是最重要的.抑制了EGFR的发生.它具有抗菌活性,具有抗菌活性.抗病毒预测的预测.灭症 (apoptosis) 是一种死亡的过程.分子对接的分子对接.分子动力学分子动力学皮里多皮里米丁的衍生品.伤口愈合测试试验方法

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