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 c...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.展开更多
基金Excellent Discipline Cultivation Project of Jianghan University (2023XKZ006)Four New Disciplines Special Project of Jianghan University(2022SXZX02)Jianghan University Research Projects(2023zd037,2024zd043,2024yb105)。
文摘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.
