Novel Schiff base-Pt(ii) complexes: inhibition of Aβ aggregation via histidine interaction

Abstract

In this study, three Schiff base ligands (L1–L3) and their novel platinum(II) complexes (I–III) were synthesized and characterized using FT-IR, NMR, and elemental analysis. The crystal structure of complex I was determined by X-ray crystallography, while the lipophilicity of the complexes was evaluated by UV-Vis spectroscopy. The ability of the compounds to inhibit Aβ aggregation was assessed using the SH-SY5Y human neuroblastoma cell line. Due to its high cytotoxicity, comparable to that of cisplatin, complex II was excluded from further biological investigations. The kinetics of Aβ aggregation inhibition were examined fluorometrically using Thioflavin-T, and the binding interactions of the complexes with the Aβ_1–42 sequence were elucidated through studies of their interactions with L-histidine using ¹H-NMR and LC/QTOF/MS analyses. The results demonstrate that complexes I and III significantly suppress Aβ fibril formation, with IC₅₀ values of 50 µM and 25 µM, respectively. The enhanced biological activity is attributed to the strong electron-donating properties of the ligand substituents. Overall, these findings reveal that the synthesized complexes effectively inhibit Aβ amyloid aggregation and promote cell viability.