Targeting EGFR Kinase Inhibitor by Novel Naphthalene-1,2,3-Triazole Hybrids <i>via</i> Click Chemistry: Synthesis, Cell-Cycle Arrest, Apoptosis, and <i>In Silico</i> Studies

A series of heterocyclic naphthalene-1,2,3-triazole derivatives (<b>12–21)</b> were synthesized <i>via</i> a click reaction, resulting in high yields (83–93%). The cytotoxic effects of these derivatives were investigated on HCT-116, HePG-2, and MCF-7 cancer cell lines. Compound <b>20</b> exhibited the greatest level of activity against the tested cell lines, showing significant selectivity for tumor cells. Treatment with compound <b>20</b> on breast cancer cells led to increased early and late apoptosis, necrosis, and enhanced cell aggregation during the G2/M phase, resulting in a 36.18% cellular percentage. Compound <b>20</b> also displayed significant EGFR inhibitory activity, comparable to erlotinib’s IC₅₀, suggesting its potential for developing new breast cancer treatments. Molecular docking revealed a specific interaction between compound <b>20</b> and the binding pocket of EGFR. These results indicate that compound <b>20</b> could be a promising candidate for further development in cancer therapy.