Differential response of HER2 - and HER2 + breast cancer cells to quinazoline and triazole derivatives: advancing receptor subtype-specific phytochemical targeting.

The current targeted therapies have limitations in treating HER2 - and HER2 + breast cancer subtypes, and investigating molecular pathways offers new avenues for effective treatment strategies. This study integrates the computational and biological assays to evaluate the differential anticancer potential of Quinazoline and Triazole derivatives for receptor-specific (HER2- and HER2 +) mechanisms in breast cancer. The predicted binding energies and interaction profiles, obtained from molecular docking and dynamic simulation studies, suggested distinct affinity patterns: F0922-0471 (ER > PR > HER2) and F2865-0609 (HER2 > ER = PR). Furthermore, these compounds exhibit receptor-ligand interaction patterns similar to those of FDA-approved drugs. ADMET profiling revealed the favorable drug-like properties and low toxicity, suggesting a non-carcinogenic and acceptable safety profile. In vitro studies demonstrated that both compounds caused significant cell death in HER2 - (MCF-7) and HER2 + (SKBR3) breast cancer cells, though through distinct cell cycle and ROS responses. The HER2 - cells showed a greater reduction in ER expression with the quinazoline derivative (F0922-0471) than with the triazole derivative, which significantly reduced HER2 expression in HER2 + cells, underscoring their receptor-specific effects. This study concludes that Quinazoline (F0922-0471) and Triazole derivatives (F2865-0609) show potential as receptor-specific, multi-targeted anticancer agents for distinct breast cancer subtypes, warranting further preclinical and clinical evaluations.