Marudupandiyar College (Affiliated to Bharathidasan University), Thanjavur - 613403, Tamilnadu, India.
Department of Biotechnology, Bharath Institute of Higher Education and Research, Chennai - 600073, Tamilnadu, India.
Asian Pac J Cancer Prev. 2022 May 1;23(5):1687-1697. doi: 10.31557/APJCP.2022.23.5.1687.
Abnormal expression of EGFR (epidermal growth factor receptor) results in different types of human tumors. Quinazoline-containing derivative signify an attractive platform for EGFR inhibitors. The present study aims to discover the potential binders of a group of compounds belonging to oxazolo[4,5-g]quinazoline-2(1H)-one derivative as EGFR inhibitors.
We apply multiple computational procedures, including pharmacophore-based virtual screening methods, to perform a preliminary screening against EGFR over compounds belonging to oxazolo[4,5-g]quinazoline-2(1H)-one derivative. Then, we carried a fine screening by molecular dynamics simulations, followed by free energy calculations.
The best pharmacophore model created has five characteristics. Three hydrogen bonds acceptors (A) and two aromatic rings (R) make up AAARR (a sequential representation of chemical features of ligands). We have performed pharmacophore-based screening with different databases like Asinex, Chembridge, Lifechemicals, Maybridge, Specs, and Zinc. Top-scoring 30 molecules were considered for performing induced fit docking. Molecular Dynamics Simulations executed for the top five ligands confirmed that throughout the simulation, the protein-ligand complexes remained stable.
Thus, the results obtained from this research provide insights for the development of oxazolo[4,5-g]quinazoline-2(1H)-one derivative as potent EGFR inhibitors.
表皮生长因子受体（EGFR）的异常表达导致了人类的不同类型肿瘤。含喹唑啉的衍生物是 EGFR 抑制剂的一个有吸引力的平台。本研究旨在发现一组属于噁唑并[4,5-g]喹唑啉-2（1H）-酮衍生物的化合物作为 EGFR 抑制剂的潜在配体。
我们应用多种计算程序，包括基于药效团的虚拟筛选方法，对属于噁唑并[4,5-g]喹唑啉-2（1H）-酮衍生物的化合物对 EGFR 进行初步筛选。然后，我们通过分子动力学模拟进行精细筛选，然后进行自由能计算。
创建的最佳药效团模型具有五个特征。三个氢键受体（A）和两个芳环（R）构成 AAARR（配体化学特征的顺序表示）。我们已经使用不同的数据库（如 Asinex、Chembridge、Lifechemicals、Maybridge、Specs 和 Zinc）进行了基于药效团的筛选。考虑对得分最高的 30 个分子进行诱导契合对接。对前五个配体进行的分子动力学模拟证实，在整个模拟过程中，蛋白质-配体复合物保持稳定。
因此，本研究的结果为开发噁唑并[4,5-g]喹唑啉-2（1H）-酮衍生物作为有效的 EGFR 抑制剂提供了思路。
