In this study, we designed and synthesized a number of novel pyrido[3,4-d]pyrimidine-thiazolidine-1,2,4-oxadiazole derivatives and investigated them in vitro for their inhibitory action toward epidermal growth factor receptor (EGFR) kinases and antiproliferative activity against two different cell lines, MCF-7 and A-549. When compared to the lead chemicals, 5-fluorouracil and erlotinib, some of the compounds demonstrated acceptable activity. Among them, the most promising compounds 4d and 4e displayed potent anticancer activity against both MCF-7 and A-549 cell lines (IC₅₀ values remaining: 1.97 ± 0.28 μM to 8.14 ± 0.52 μM, respectively); the comparative IC₅₀ values for 5-fluorouracil and erlotinib in these cell lines were 5.56 ± 0.34 μM, 12.66 ± 0.76 μM, and 3.64 ± 0.49 μM, 9.54 ± 0.75 μM, respectively; as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.34 ± 0.07 μM and 0.42 ± 0.06 μM) were more effective than the conventional drug Erlotinib (IC₅₀ = 0.42 ± 0.02 μM).

中文翻译：

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新型吡啶并[3,4-d]嘧啶-噻唑烷-1,2,4-恶二唑的合成作为有效的EGFR靶向抗癌药物


在本研究中，我们设计并合成了许多新型吡啶并[3,4-d]嘧啶-噻唑烷-1,2,4-恶二唑衍生物，并在体外研究了它们对表皮生长因子受体（EGFR）激酶的抑制作用以及针对两种不同细胞系 MCF-7 和 A-549 的抗增殖活性。与主要化学品 5-氟尿嘧啶和厄洛替尼相比，一些化合物表现出可接受的活性。其中，最有前途的化合物4d和4e对MCF-7和A-549细胞系均表现出有效的抗癌活性（剩余IC ₅₀ 值分别为：1.97±0.28μM至8.14±0.52μM）； 5-氟尿嘧啶和厄洛替尼在这些细胞系中的比较 IC ₅₀ 值分别为 5.56 ± 0.34 μM、12.66 ± 0.76 μM 和 3.64 ± 0.49 μM、9.54 ± 0.75 μM；以及优异的激酶抑制活性（EGFR：IC ₅₀ = 0.34 ± 0.07 μM 和 0.42 ± 0.06 μM），比传统药物厄洛替尼（IC ₅₀ = 0.42 ± 0.02）更有效微米）。