A comprehensive biophysical and theoretical study on the binding of dexlansoprazole with human serum albumin

Pharmacokinetics, pharmacodynamics, and therapeutic activity of drugs are defined by the affinities between the drug and biological macromolecules through molecular recognition. The present work is on the investigation of the interaction of new generation competent proton pump inhibitor dexlansopra-zole (DLP) with human serum albumin (HSA). Fluorescence and UV-visible spectroscopy studies were adopted for quantification of the interaction in terms of the quenching constant (KSV), bimolecular quenching constant (Kq), equilibrium-binding constant (Kb), the number of binding sites (n), and the ther-modynamic parameters. A hypochromic effect on the addition of HSA to DLP from the absorption studies shows their interaction. The quenching and binding constants from fluorescence studies were 104 and 105 M-1 order, respectively. A higher quenching constant with increasing temperature reflects a collisional-type quenching mechanism. A higher binding constant at a higher temperature shows an increase in the rate of binding, and the negative value of the free energy change shows the spontaneity of the binding. The sign and magnitude of the change in entropy (DS0 = 737.12 +/- 2 J mol-1 K-1) and enthalpy (DH0 = 193.58 +/- 1.7 kJ mol-1) shows that binding is an entropy-driven process with hydropho-bic force as the major driving force. Site marker competitive displacement studies using 1-Anilino-8-naphthalene sulfonate (ANS), warfarin, and ibuprofen confirmed the biding of DLP in subdomain IIA of HSA. Binding-induced structural changes were evident from the changes in the circular dichroism (CD) signatures. Molecular docking of DLP in HSA showed the position of DLP in the warfarin binding site of HSA and corroborated the experimental findings.(c) 2023 Elsevier B.V. All rights reserved.

Automated summary

The present study investigates the interaction between the new generation proton pump inhibitor dexlansoprazole (DLP) and human serum albumin (HSA). Fluorescence and UV-visible spectroscopy were used to quantify the interaction and determine parameters such as quenching constant, binding constant, and thermodynamic parameters. The results show that DLP and HSA interact with a hypochromic effect observed in absorption studies. The binding constants obtained from fluorescence studies indicate a collisional-type quenching mechanism. The study also confirms the binding of DLP in subdomain IIA of HSA through site marker competitive displacement studies and molecular docking.