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 mu M to 8.14 +/- 0.52 mu M, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cell lines were 5.56 +/- 0.34 mu M, 12.66 +/- 0.76 mu M, and 3.64 +/- 0.49 mu M, 9.54 +/- 0.75 mu M, respectively; as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.34 +/- 0.07 mu M and 0.42 +/- 0.06 mu M) were more effective than the conventional drug Erlotinib (IC50 = 0.42 +/- 0.02 mu M).