Unraveling the Anticancer Efficacy and Biomolecular Properties of Ru(II)-Arene Complexes of Pyrene-Based Thiosemicarbazone Ligands: A Comprehensive In Silico/In Vitro Exploration

We report the successful synthesis and comprehensive characterization of novel Ru­(II)-arene complexes incorporating pyrene-based thiosemicarbazone (TSC) ligands. Utilizing a suite of advanced spectroscopic techniques including ultraviolet–visible (UV–visible), Fourier transform infrared (FT-IR), 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS), the intricate structural and electronic nuances of these complexes were elucidated. X-ray crystallographic data unequivocally affirmed the ligands’ preferential coordination through the thionyl sulfur and imine nitrogen moieties with the Ru­(II) ion. Rigorous density functional theory (DFT) computations reveal these complexes as exemplary electron donors, concomitantly hinting at their significant bioactive potential. Notably, molecular docking and molecular dynamic simulation studies suggest that they are potential SND1 protein inhibitors, which are essential proteins in the functioning of cancer cells. Furthermore, they have a strong affinity for binding to CT-DNA and bovine serum albumin (BSA), indicating DNA intercalation and a strong protein-binding ability. Intriguingly, the Ru-arene TSC complexes unveiled potent cytotoxic activity against an array of cancerous cell linesmost notably MDA-MB-231 (IC50 = 10.2 ± 0.02 μM), A549 (IC50 = 25.7 ± 0.07 μM), and HeLa (IC50 = 20.7 ± 0.05 μM) for RuP2P emerging as a standout agent.