Synthesis of novel pyrido[3,4-d]pyrimidine-thiazolidione-1,2,4-oxadiazoles as potent EGFR targeting anticancer agents

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).