Ruthenium(II) Schiff Base Complexes With 9‐Formyl‐8‐Hydroxyjulolidine: From Synthesis to Anticancer Insights

ABSTRACT

Two hydrazone‐based Schiff base ligands were synthesized through condensation reaction between 9‐formyl‐8‐hydroxyjulolidine and 2‐hydrazinobenzothiazole or 2‐hydrazinoquinoline. These ligands were subsequently coordinated to the precursor complex [RuHCl(CO)(EPh₃)₃] (E = P or As), yielding a new family of Ru(II) complexes with the general formula [RuH(CO)(EPh₃) ₂ L] ( C1–C4 ) (E = P or As; L = 9‐formyl‐8‐hydroxy‐julolidine‐derived hydrazone ligands). Micro analyses and many spectroscopic methods, such as FT‐IR, UV–Vis, NMR spectroscopy, and electrospray ionization (ESI) mass spectrometry, were used to conform the formation of ligands and their associated Ru(II) complexes. Solid‐state structure analysis of complexes ( C1 and C3 ) confirmed distorted octahedral coordination geometries around the Ru(II) center. To assess the biological potential relevance of the newly synthesized complexes, molecular docking studies were first performed, which revealed favorable binding interactions with the selected target proteins. Additionally, intermolecular interactions in the crystalline state were investigated using Hirshfeld surface analysis and two‐dimensional fingerprint plots, which revealed H···H contacts as the main contribution. The in vitro antiproliferative properties of the Ru(II) complexes were assessed against a noncancerous cell line (MCF‐10A) and two cancer cell lines (MCF‐7 and HepG‐2). The results demonstrated pronounced anticancer activity relative to cis platin, with complex C2 exhibiting exceptional cytotoxicity toward HepG‐2 cells. Furthermore, flow cytometry study revealed that treatment with complex C3 predominantly induced late apoptosis in HepG‐2 cells, whereas complex C2 primarily triggered early apoptotic cell death.