Akademik Veri Yönetim Sistemi
INORGANIC CHEMISTRY COMMUNICATIONS, cilt.184, 2026 (SCI-Expanded, Scopus)
In this study, three novel palladium(II) complexes based on S-methylthiosemicarbazone ligands derived from 1,3-butanedione and 2,4-pentanedione-functionalized with methyl (CH3), trifluoromethyl (CF3), and thiophene groups-were synthesized and structurally characterized by spectroscopic methods and single-crystal X-ray diffraction. To evaluate their potential as VEGFR-2 inhibitors, a comprehensive computational investigation was performed. Molecular docking and molecular dynamics (MD) simulations were employed to assess the binding affinities and dynamic stability of the co-ligand (colig) and three complexes (comp1, comp2, and comp3) with the VEGFR-2 receptor (PDB ID: 3CJG). Binding analyses consistently identified colig as the most potent binder, exhibiting the most favorable binding free energy (triangle G(bind) of -106.282 kJ/mol). MD simulations revealed two distinct stability profiles: colig and comp1 formed highly stable and rigid complexes, confirmed by low RMSD and RMSF values. In contrast, comp2 and comp3 were found to be significantly more flexible. Per-residue energy decomposition revealed that this stability is achieved through two different mechanisms: superior van der Waals interactions for colig, and a powerful electrostatic anchor with ASP1044 for comp1. Additionally, MTT assays on HUVEC cells revealed low cytotoxicity (IC50 > 50 mu M) for all synthesized complexes. Considering its high dynamic stability, unique electrostatic binding mechanism, and favorable safety profile, comp1 emerges as the most promising synthesized candidate for further development. These combined findings provide valuable insights for designing next-generation palladium(II)-based VEGFR-2 inhibitors.