Human serum albumin (HSA) has a very significant role in the transport of drugs, in their pharmacokinetic and pharmacodynamic properties, as well as the unbound concentration of drugs in circulating plasma. The aim of this study was to look into the competition between tigecycline (TGC) and alkaloid (ALK) (caffeine (CAF)), and flavonoids (FLAVs) (catechin (CAT), quercetin (QUE), and diosmin (DIO)) in binding to HSA in simulated physiological conditions using multiple spectroscopic measurements and docking simulations. Fluorescence analysis was used to find the binding and quenching properties of double HSA-TGC and triple HSA-TGC-CAF/FLAV systems. The conformational change of the HSA was analyzed using synchronous fluorescence spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism. Obtained results of spectroscopic analyses indicate that triple complexes of HSA-TGC-CAF/FLAVs are formed without problems and have higher binding affinities than double HSA-TGC. In addition, TGC does not change the microenvironments around the tryptophan (Trp) and tyrosine (Tyr) residues in the presence of ALK and FLAVs. Ultimately, the binding affinity, competition, and interaction nature were explored by docking modeling. Computational outcomes are in good accordance with experimentally obtained results. Accordingly, concluding remarks may be very useful for potential interactions between common food components and drugs.

Lurasidone (LUR) is an antipsychotic drug whose interaction with human serum albumin (HSA) plays a crucial role in its pharmacokinetic and pharmacodynamic properties. A thorough understanding of LUR’s binding mechanism to HSA is crucial for predicting its transport, distribution, and potential drug interactions. Methods: The interaction between LUR and HSA was investigated using fluorescence and circular dichroism (CD) spectroscopy, followed by molecular docking simulations. Binding characteristics were analyzed through quenching mechanisms, thermodynamic parameters, and competitive site marker experiments. Results: This study revealed a systematic decrease in HSA fluorescence intensity with increasing LUR concentration, indicating a static quenching mechanism driven by non-fluorescent complex formation. Binding constants suggest enhanced complex stability at higher temperatures, with thermodynamic analysis confirming an endothermic, hydrophobic interaction. Competitive site marker assays and synchronous fluorescence spectra confirmed that LUR primarily binds to site I (subdomain IIA) near tryptophan residues. Conformational changes in HSA, observed as a decrease in α-helix content, further demonstrate the structural impact of LUR binding. Conclusions: These findings offer key insights into the molecular interactions between LUR and HSA, enhancing our understanding of LUR’s pharmacokinetics and its potential interactions with other drugs. Understanding these binding characteristics can aid in optimizing LUR’s clinical application and predicting possible interactions with other biomolecules.