Abstract
The present study investigated the effect of certain 1,3,5‑triazine derivatives on epidermal growth factor receptor‑tyrosine kinase (EGFR‑TK). The results suggested that 1,3,5‑triazine derivatives exhibited optimal drug likeness via molinspiration and proved to be effective drug candidates as potential anticancer agents. The molecules were demonstrated to interact with key catalytic residues of EGFR, including Asn818, Lys721, Leu694, Val702 and Met742 as demonstrated in molecular docking experiments. Compound 1d was demonstrated to be the most potent analogue with an inhibitory constant of 0.44 nM, against EGFR‑TK in in‑vitro enzyme inhibition assay. Compound 1d was further evaluated for its effect on the cellular viability of three breast cancer cell lines, including highly metastatic MDAMB231, human epidermal growth factor receptor 2‑positive BT474 and estrogen receptorpositive MCF7 cells, using an MTT assay and apoptosis analysis. Western blot analysis was performed to examine the levels of β‑catenin in the control and treated cells. Based on the findings of the current study, the chemical 1,3,5‑triazine series are potential novel inhibitors of EGFR‑TK and β‑catenin signaling, and may be potent anti‑breast cancer agents.