Certain ruthenium compounds are found to be potent growth inhibitors for cancer cells. In the current study, a novel ruthenium-triphenylphosphine (PPh3) cation and silver-2-mercapto nicotinate acid (H2mna) anion complex (RSC) was synthesized, and its molecular structure was determined by IR, NMR and X-ray crystallography. Biological assays revealed that RSC strongly inhibited the viability of MCF-7 and MDA-MB-231 cells with IC50 values of 9.6±1.1 and 7.5±0.8 µM, respectively, and significantly blocked their migration rates. Ultraviolet spectroscopy and fluorescence emission experiments demonstrated that RSC interacted with BSA, but not DNA. Further studies on [Ag6(Hmna)2(mna)4]4- binding with BSA and DNA found the anion did not interact with these biomolecules, indicating that RSC exerted its biological functions through its ruthenium-PPh3 complex (RTC) moiety, and molecular docking provided additional evidence supporting this result. Fluorescence resonance energy transfer showed that the number of binding sites (n) and binding constant of RTC-BSA complex were 1 and 8.60 × 104 M-1 at 310K, suggesting a strong interaction between RTC and BSA. The thermodynamic parameters ΔG0, ΔH0 and ΔS0 of the binding were calculated, and it was demonstrated that the binding of RTC with BSA was enthalpy-driven, and the main forces between RTC and BSA were electrostatic force and hydrogen bonding. Molecular docking showed that the binding site of BSA with RSC was located on the interface between the domains IIA and IIB of the protein. The present study sheds light on that a ruthenium mono-coordinated with PPh3 complex could help to design and develop a new class of antitumor drugs.
Keywords: Antitumor activity; Crystal structure; Molecular docking; Pharmacophore analysis; Ruthenium-silver complex; Ultraviolet and fluorescence spectroscopy.
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