Abstract
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.
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•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