Design, synthesis and anticancer evaluation of novel half-sandwich Ru(II) complexes bearing pyrazalone moiety: Apoptosis inducers based on mitochondrial dysfunction and G0/G1 arrest

J Inorg Biochem. 2023 Oct 28;250:112421. doi: 10.1016/j.jinorgbio.2023.112421. Online ahead of print.ABSTRACTSix half-sandwich Ru(II) complexes (Ru1-Ru6), integrated with 5-phenyl-2-(pyridin-2-yl)-2,4-dihydro-3H-pyrazol-3-one (PDPO1-PDPO6) ligands, were synthesized and spectroscopically characterized. The structure of Ru3 that crystallized as a monoclinic crystal with P21/c space group was further confirmed by X-ray single crystal diffraction. Prototropic tautomerism within the complexes transformed OH-form ligands to NH-form, forming a hydrogen bond (Cl1---H-N3). The complexes and ligands' cytotoxicity was assessed against several cancerous (HepG2, A549, MCF-7) and normal Vero cell lines. Relative to the ligands and Cisplatin, complexes (Ru2, Ru3, Ru5, Ru6) exhibited potent cytotoxicity against cancer cells, with IC50 values from 2.05 to 15.69 μM/L, excluding Ru1 and Ru4. Specifically, Ru2, Ru3, and Ru5 demonstrated superior anti-HepG2 properties. Compared to Cisplatin, Ru2 and Ru5 were less toxic to Vero cells, highlighting their enhanced selectivity in toxicity. Structure-activity relationship (SAR) studies indicated that t-butyl substitution (in Ru2) or -Cl (in Ru5) on the benzene ring significantly improved the selective toxicity. These complexes manifested substantial lipophilicity, cellular uptake, and were quickly hydrolyzed to Ru-H2O species. Roughly positive correlations were observed between hydrolysis rate, lipophilicity, cellular uptake, and anticancer activitie...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Source Type: research