Synthesis of novel pyrido[2,3-d]pyrimidine-thiazolidine-1,2,3-triazoles: Potent EGFR targeting anticancer agents

•This study aims to design and synthesize pyrido[2,3-d]pyrimidine-thiazolidine-1,2,3-triazoles (4a-4o) via ‘click’ chemistry.•Novel 1,2,3-triazoles exhibited anti-cancer activity and epidermal growth factor receptor (EGFR) was carried out for potent compounds.•In silico ADME and molecular docking studies were also held potent compounds for the future anticancer drug discovery initiatives.•The compound 4e showed greater potency than the standard drug Erlotinib. In this study, we designed and synthesized a number of novel pyrido[2,3-d]pyrimidine-thiazolidine-1,2,3-triazole derivatives and investigated them in vitro for their inhibitory action toward EGFR kinases and anti-proliferative activity against two different cell lines. When compared to the lead chemical, erlotinib, the majority of the compounds demonstrated acceptable activity. Among them, the most promising compounds 4d and 4e exhibited excellent anti-proliferative activity against the MCF-7 cancer cell line with IC50 values of 4.19 ± 0.24 and 3.52 ± 0.12 µM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.53 ± 0.02 and 0.39 ± 0.03 µM). In silico docking studies were performed to evaluate the molecular interactions of 4a-4o compounds with the human epidermal growth factor receptor, EGFR (PDB: 1M17) proteins with a co-crystallized ligand (erlotinib) and observed that four of the compounds (4d, 4e, 4m, and 4o) had appreciable binding energies compared to the standard drug erlotinib. Finally, the in silico pharmacokinetic profile was predicted for potent compounds 4d, 4e, 4m, and 4o using SWISS/ADME, where the 4m and 4o compounds had a better profile compared to the 4d and 4e compounds.