Targeting Breast Cancer with Triazine Derivatives: A Molecular Docking Analysis of Her2 and Parp1 Inhibition

Background: Heterocyclic compounds, particularly triazines, have significant attention in pharmaceutical and industrial research due to their broad spectrum of biological activities. Objective: This study focuses on the synthesis and molecular docking analysis of 15 novel triazine derivatives (TCT1-TCT15) to evaluate their potential as inhibitors of two critical cancer-related targets: human epidermal growth factor receptor 2 (HER2) and poly (ADP-ribose) polymerase 1 (PARP1). Materials and Methods: The derivatives were synthesized by reacting 2,4,6-Trichloro- 1,3,5-Triazine (TCT) with various aldehydes, thereby incorporating diverse substituent groups. Molecular docking was conducted using AutoDock 1.5.5, and protein-ligand interactions were visualized through Chimera software. Results: The docking results revealed strong binding affinities of the synthesized compounds to both HER2 and PARP1. For HER2, TCT9 (-12.73 kcal/ mol), TCT4 (-12.47 kcal/mol), and TCT5 (-12.34 kcal/mol) showed the most favorable binding energies, all with inhibition constants in the nanomolar range. For PARP1, TCT13 (-13.96 kcal/ mol), TCT12 (-13.64 kcal/mol), and TCT4 (-13.33 kcal/mol) demonstrated superior binding interactions, surpassing those of standard inhibitors. Structural analysis indicated that the presence of electron-withdrawing groups such as -Cl and -NO₂, as well as electron-donating groups like -OH and -OCH₃, significantly influenced the binding efficacy of the compounds. Stabilization of the protein-ligand complexes was primarily mediated by hydrogen bonding and hydrophobic interactions. Conclusion: These findings suggest that the synthesized triazine derivatives, particularly TCT9, TCT13, and TCT4, exhibit strong potential as anticancer agents, warranting further in vitro and in vivo investigations to explore their clinical applicability.