The most dangerous subtype of breast cancer, triple-negative breast cancer (TNBC), accounts for 25% of all breast cancer-related deaths and 15% of all breast cancer cases. TNBC is distinguished by the lack of immunohistochemical expression of HER2, progesterone receptors, or oestrogen receptors. Although it has been reported that upregulation of EGFR and VEGFR-2 is associated with TNBC progression, no proven effective targeted therapy exists at this time. We used structural bioinformatics methods, including density functional theory, molecular docking, molecular dynamic simulation, pharmacokinetic and drug-likeness models, to identify promising EGFR/VEGFR-2 inhibitors from N-(4-methoxyphenyl)-2-[4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy] acetamide and six of its modified derivatives in light of the lack of effective targets inhibitor Version 14 of Spartan software was used to analyse density functional theory. The Schrodinger software suite 2018’s Maestro interface was used for the molecular docking analysis, and the admetSAR and swissADME servers were used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity. All of the compounds showed strong electronic characteristics. Additionally, all of the tested compounds met the ADMET and drug-likeness requirements without a single instance of Lipinski’s rule of five violations. Additionally, the molecules’ levels of affinity for the target proteins varied. The highest binding affinities were demonstrated by the MOLb-VEGFR-2 complex (− 9.925 kcal/mol) and the MOLg-EGFR complex (− 5.032 kcal/mol). The interaction of the molecules in the domain of the EGFR and VEGFR-2 receptors was also better understood through molecular dynamic simulation of the complex.

最危险的乳腺癌亚型是三阴性乳腺癌 (TNBC)，占所有乳腺癌相关死亡的 25% 和所有乳腺癌病例的 15%。TNBC 的特点是缺乏 HER2、孕激素受体或雌激素受体的免疫组织化学表达。尽管有报道称 EGFR 和 VEGFR-2 的上调与 TNBC 进展相关，但目前尚无经证实有效的靶向治疗。我们采用结构生物信息学方法，包括密度泛函理论、分子对接、分子动力学模拟、药代动力学和类药性模型，从 N-(4-methoxyphenyl)-2-[4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy] 乙酰胺及其六种改性衍生物中鉴定有前途的 EGFR/VEGFR-2 抑制剂鉴于缺乏有效的目标抑制剂，使用 Spartan 软件版本 14 来分析密度泛函理论。Schrodinger 软件套件 2018 的 Maestro 界面用于分子对接分析，admetSAR 和 swissADME 服务器用于药物相似性和吸收、分布、代谢、排泄和毒性。所有的化合物都显示出很强的电子特性。此外，所有受试化合物均符合 ADMET 和类药性要求，没有一例违反 Lipinski 的五次规则。此外，分子对靶蛋白的亲和力水平各不相同。MOLb-VEGFR-2 复合物 (− 9.925 kcal/mol) 和 MOLg-EGFR 复合物 (− 5.032 kcal/mol) 证明了最高的结合亲和力。通过复合物的分子动力学模拟，也更好地了解了 EGFR 和 VEGFR-2 受体结构域中分子的相互作用。