炎症与癌症之间的密切联系激发了一系列6-甲氧基萘的1,3,4-恶二唑衍生物（化合物H4-A-F）的合成。利用傅里叶变换红外、质子核磁共振、碳13核磁共振波谱技术和CHN分析验证了新化合物的化学结构。使用计算机辅助药物设计方法来预测化合物的生物靶点、ADMET性质、毒性，并评估设计化合物与标准表皮生长因子受体（EGFR）抑制剂厄洛替尼之间的分子相似性。通过3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴化物测定、细胞周期分析、显微镜凋亡检测、定量逆转录-聚合酶链反应、免疫印迹和 EGFR 酶抑制测定。新恶二唑衍生物的计算机分析表明，这些化合物靶向 EGFR，并且化合物 H4-A、H4-B、H4-C 和 H4-E 显示出与厄洛替尼相似的分子特性。此外，结果表明合成的化合物均不具有致癌性，并且化合物H4-A、H4-C和H4-F是无毒的。化合物H4-A显示出针对EGFR药效团模型的最佳拟合得分，然而，体外研究表明化合物H4-C是最具细胞毒性的。化合物 H4-C 通过诱导细胞凋亡和坏死而对 HCT-116 结直肠癌细胞产生细胞毒性。此外，化合物H4-D、H4-C和H4-B对EGFR酪氨酸激酶具有与厄洛替尼相当的强效抑制作用。本次调查的结果为进一步研究合成化合物与厄洛替尼之间的差异提供了基础。然而，需要进行额外的测试来评估所有这些差异并确定最有希望进行进一步研究的化合物。© 2024 Wiley periodicals LLC。

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.© 2024 Wiley Periodicals LLC.