光谱法研究具有细胞毒性活性的铂-苯并噁唑杂化剂及其三齿螯合铂单元与人血清白蛋白的相互作用OA

Interactions between platinum complexes and human serum albumin(HSA)play crucial roles in the bioavailability and toxicology of platinum-based anticancer drugs.Platinum-intercalator hybrid pharmacophores are a novel class of DNA-targeted cytotoxic agents that show potent activity across a broad range of solid tumor cell lines.In this study,the interactions of a cytotoxic Pt-benzoxazole hybrid agent,[PtLCl]Cl(1,where L=N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-(bis(2-ethylthioethyl)amino)acetamide)and its tridentate chelating platinum unit,[PtL′Cl]Cl(2,where L′=bis(2-ethylthioethyl)amine),with HSA were investigated by multiple spectroscopic methods.The results revealed that both complexes exhibited moderate HSA binding affinity(1>2),triggering conformation and microenvironmental changes of the protein and suppressing its intrinsic fluorescence via static quenching pathways.The thermodynamic parameters(ΔG°,ΔH°,ΔS°)calculated from fluorescence data at different temperatures suggested that the binding reaction between the complexes and HSA was a spontaneous process dominated by hydrophobic interactions.The binding site number indicated 1∶1 stoichiometry for both complexes at a single primary binding site on HSA.Furthermore,site marker competition assays demonstrated that complexes 1 and 2 could bind to the drug binding sites I(bromophenol blue-binding domain)and site II(ibuprofen-binding domain)on HSA,respectively.