Revealing the Anti-Cancer Potential of 1,2,3-Triazole-Isonicotinate Derivatives Targeting EGFR Kinase Inhibition in MCF-7 Cancer Cells: Design, Synthesis, Biological Evaluation, and In Silico Studies

Click chemistry was used to synthesize a new library of 1,2,3-triazole-isonicotinate derivatives 8–13 using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between mono- or bis 2,6-ethynylisonicotinate 3,4, and aromatic azides derivatives 5–7 with high yields (89–96%). These compounds were evaluated for their antiproliferative activity against hepatocellular carcinoma (Hep-G2), breast cancer (MCF-7), and colon cancer (HCT-116) cell lines, alongside a healthy non-cancerous skin fibroblast cell line (BJ-1). As compared with the reference drug, all new triazole-isonicotinate compounds have significantly greater cytotoxicity against colon and breast cancer cells, while compounds 13 and 10 have moderate cytotoxicity against liver cancer cells. The molecular docking study correlates the compound’s biological activity with its ability to establish stable interactions with protein-ligand complexes in the relevant biological targets. Compound 13 demonstrated a strong ability to induce apoptosis and cause cell cycle arrest in MCF-7 cells, along with significant inhibitory activity against the epidermal growth factor receptor (EGFR). These preliminary findings suggest that 1,2,3-triazole-isonicotinate derivatives, particularly compound 13, hold potential as candidates for further investigation as anticancer agents for breast cancer treatment.