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The interaction between erlotinib (ERL) and bovine serum albumin (BSA) was studied in the presence of quercetin (QUR), a flavonoid with antioxidant properties. Ligands bind to the transport protein BSA resulting in competition between different ligands and displacing a bound ligand, resulting in higher plasma concentrations. Therefore, various spectroscopic experiments were conducted in addition to in silico studies to evaluate the interaction behavior of the BSA-ERL system in the presence and absence of QUR. The quenching curve and binding constants values suggest competition between QUR and ERL to bind to BSA. The binding constant for the BSA-ERL system decreased from 2.07 × 10 4 to 0.02 × 10 2 in the presence of QUR. The interaction of ERL with BSA at Site II is ruled out based on the site marker studies. The suggested Site on BSA for interaction with ERL is Site I. Stability of the BSA-ERL system was established with molecular dynamic simulation studies for both Site I and Site III interaction. In addition, the analysis can significantly help evaluate the effect of various quercetin-containing foods and supplements during the ERL-treatment regimen. In vitro binding evaluation provides a cheaper alternative approach to investigate ligand-protein interaction before clinical studies.

In addition, drug-protein interactions, drug-drug interaction mechanisms, anti-glycating and antioxidant activity, binding affinity, network-pharmacology-driven investigations, and targeted anticancer treatments were also investigated. In addition, because the aim of rational drug design is to make use of knowledge of the structural data and protein-ligand binding mechanisms to optimize the process of finding new drugs, an in-depth understanding of the nature of molecular recognition/interactions is also of great importance. 35164061 4 Wani T.A., Alanazi M.M., Alsaif N.A., Bakheit A.H., Zargar S., Alsalami O.M., Khan A.A. Interaction Characterization of a Tyrosine Kinase Inhibitor Erlotinib with a Model Transport Protein in the Presence of Quercetin: A Drug-Protein and Drug-Drug Interaction Investigation Using Multi-Spectroscopic and Computational Approaches. [Extracted from the article]

Quetiapine (QTP) is a short-acting atypical antipsychotic drug that treats schizophrenia or manic episodes of bipolar disorder. Human serum albumin (HSA) is an essential transport protein that transports hormones and various other ligands to their intended site of action. The interactions of QTP with HSA and their binding mechanism in the HSA-QTP system was studied using spectroscopic and molecular docking techniques. The UV-Vis absorption study shows hyperchromicity in the spectra of HSA on the addition of QTP, suggesting the complex formation and interactions between QTP and HSA. The results of intrinsic fluorescence indicate that QTP quenched the fluorescence of HSA and confirmed the complex formation between HSA and QTP, and this quenching mechanism was a static one. Thermodynamic analysis of the HSA-QTP system confirms the involvement of hydrophobic forces, and this complex formation is spontaneous. The competitive displacement and molecular docking experiments demonstrated that QTP is preferentially bound to HSA subdomain IB. Furthermore, the CD experiment results showed conformational changes in the HSA-QTP system. Besides this, the addition of QTP does not affect the esterase-like activity of HSA. This study will help further understand the credible mechanism of transport and delivery of QTP via HSA and design new QTP-based derivatives with greater efficacy. [ABSTRACT FROM AUTHOR]

Flavonoid-containing food supplements are widely used as antioxidants, and the continuous use of these supplements with other drugs can lead to clinically significant interactions between these and other drugs. The medications in systemic circulation are mainly transported by serum albumin, a major transport protein. This study evaluated the interactions of rutin (RUT), naringenin (NAR), and sinapic acid (SIN) with the most abundant transport protein, bovine serum albumin (BSA), and the anticancer drug, the tyrosine kinase inhibitor Erlotinib (ETB), using various analytical methods. Interaction between multiple types of ligands with the transport proteins and competition between themselves can lead to the bound ETB's displacement from the BSA-binding site, leading to elevated ETB concentrations in the systemic circulation. These elevated drug fractions can lead to adverse events and lower tolerance, and increased resistance to the therapeutic regimen of ETB. The experimental and computational methods, including molecular-docking studies, were used to understand the molecular interactions. The results suggested that the complexes formed were utterly different in the binary and the ternary system. Furthermore, comparing the ternary systems amongst themselves, the spectra differed from each other. They thus inferred that complexes formed between BSA-ETB in the presence of each RUT, NAR, and SIN separately were also different, with the highest value of the reduction in the binding energy in RUT, followed by SIN and then NAR. Thus, we conclude that a competitive binding between the ETB and these flavonoids might influence the ETB pharmacokinetics in cancer patients by increasing ETB tolerance or resistance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Olmutinib is used to treat non-small cell lung cancer (NSCLC). • Colchicine, an antimitotic drug, has considerable toxicity. • Plasma protein binding plays a significant role in the pharmacokinetics of drugs. • Colchicine and olmutinib can displace each other from the plasma protein binding site. • Displacement of colchicine from albumin binding site may cause toxicity. Drug-drug interactions are due to the binding of a drug to plasma proteins displacing another plasma protein-bound drug. Two ligands, olmutinib (OLM) and colchicine (COL), were explored for their binding and displacement interaction with bovine serum albumin (BSA). Olmutinib is a 3rd-generation tyrosine kinase inhibitor (TKI), inhibits EGFR. COL is an anti-mitotic agent used in the treatment of gouty arthritis and has chemotherapeutic properties. The binding of BSA with OLM and COL was evaluated independently and in the presence of each other with spectroscopic and molecular docking and molecular dynamic simulation. Results based on quenching curves, displacement curves, binding constants, and docking results were evaluated. The presence of either drug (OLM or COL) influenced the binding of OLM and COL to BSA. The OLM had a higher binding capacity to BSA compared to COL. The presence of COL in the BSA-OLM system lowered the binding constants in comparison to its binary system. The OLM in the BSA-COL system increased the binding constant values for the system compared to the BSA-COL system. These findings are essential since increased non-bound fraction or reduced free drug fraction availability in the systemic circulation. The interference in the binding of drugs may lead to adverse events or subtherapeutic responses of the drugs. [ABSTRACT FROM AUTHOR]

• Ascorbic acid or vitamin C is an antioxidant prescribed in flu infections (COVID). • Colchicine is used to treat gouty arthritis Ascorbic acid or. • Plasma protein binding plays significant role in pharmacokinetics of drugs. • Colchicine and vitamin C can displace each other from plasma protein binding site. • Effect of vitamin C was investigated on colchicine-BSA interaction. Two or more drugs are prescribed commonly to patients depending on their physical health conditions. Concomitant drugs might lead to specific drug-drug interactions with serum albumin, the main transporter protein present in the blood. This study evaluated the effect of colchicine on the binding of ascorbic acid (vitamin C) commonly prescribed in viral infections to bovine serum albumin (BSA). The interaction was evaluated using fluorescence spectroscopy, absorption spectroscopy, molecular docking, and molecular dynamic simulation. A static quenching mechanism was observed for both BSA-colchicine and BSA-ascorbic interaction. The binding constant for the BSA-ascorbic acid system decreased from 1.23 × 105 to 0.26 × 102 in the presence of colchicine, whereas the binding constant of BSA-colchicine decreased from 1.39 × 105 to 4.81 × 102 in the presence of ascorbic acid. Thus, the binding of ascorbic acid and colchicine was significantly affected in the presence of each other. Co-administration of colchicine and ascorbic acid needs to be studied further as the co-administration may lead to serious adverse events in patients taking vitamin C supplements and under treatment with colchicine. [ABSTRACT FROM AUTHOR]

The binding and displacement interaction of colchicine and azithromycin to the model transport protein bovine serum albumin (BSA) was evaluated in this study. Azithromycin, a macrolide antibiotic, has antiviral properties and hence, has been used concomitantly with hydroxychloroquine against SARS-CoV-2. Colchicine, a natural plant product is used to treat and prevent acute gout flares. Some macrolide antibiotics are reported to have fatal drug-drug interactions with colchicine. The displacement interaction between colchicine and azithromycin on binding to BSA was evaluated using spectroscopic techniques, molecular docking and molecular dynamic simulation studies. The binding constant recorded for the binary system BSA-colchicine was 7.44 × 104 whereas, the binding constant for the ternary system BSA-colchicine in presence of azithromycin was 7.38 × 104 and were similar. Azithromycin didn't bind to BSA neither did it interfere in binding of colchicine. The results from molecular docking studies also led to a similar conclusion that azithromycin didn't interfere in the binding of colchicine to BSA. These findings are important since there is possibility of serious adverse event with co-administration of colchicine and azithromycin in patients with underlying gouty arthritis and these patients need to be continuously monitored for colchicine toxicity. • Macrolide antibiotic are reported to have fatal drug-drug interaction with colchicine. • Plasma protein binding plays significant role in pharmacokinetics of drugs. • Spectroscopic, docking and MDS were used to study the in-vitro interaction. • Effect of azithromycin was investigated on colchicine-BSA interaction. • Displacement of colchicine from its binding site by azithromycin was evaluated. [ABSTRACT FROM AUTHOR]

Serum albumin is the major transporter protein present in systemic circulation and the ability to transport ligands can be influenced in presence of other ligands. This interaction can influence the pharmacodynamic and pharmacokinetic property of certain ligands. Spectroscopic and molecular docking studies were conducted to understand the poziotinib binding interaction to bovine serum albumin (BSA). Further, influence of different flavonoids (quercetin, rutin, naringenin and sinapic acid) on displacing poziotinib from BSA binding sites was also studied. The BSA and poziotinib followed a static quenching mechanism as the Stern–Volmer constant showed decrease (7.6 × 104–6.0 × 104) when the temperature increased from 298 K to 310 K. The BSA and poziotinib interaction was spontaneous and enthalpy driven. Involvement of Van der Waals forces and hydrogen bonding in the binding interaction was suggested on the basis of thermodynamic study results. Conformational changes were suggested in the BSA on its interaction with poziotinib based on fluorescence experimental data. The binding constant for BSA-poziotinib showed a maximum decrease in presence of quercetin followed by naringenin, rutin and sinapic acid respectively. Site displacement studies suggested binding of poziotinib site I of BSA. Unlabelled Image • The investigational drug poziotinib is a suitable anticancer drug candidate for EGFR TKI–resistant lung cancer cells • Plasma protein binding has a major role in drug therapy specifically the pharmacokinetics and pharmacodynamics. • The interaction between poziotinib and BSA has been investigated by using spectroscopic methods. • Effect of 4 different flavonoids was investigated on poziotinib-BSA interaction. • The experimental results will be helpful in preclinical drug development of poziotinib [ABSTRACT FROM AUTHOR]