BINDING INTERACTION OF QUINOLINE DERIVATIVES TO SERUM ALBUMIN USING MULTISPECTROSCOPY, MOLECULAR DOCKING AND MOLECULAR DYNAMICS SIMULATIONS

Abstract

The interaction between plasma proteins and drugs is crucial for understanding the pharmacodynamics and pharmacokinetics of therapeutic agents. This study examined the intermolecular interactions of both bovine serum albumin (BSA) and human serum albumin (HSA) with two newly synthesized 2,4-disubstituted quinoline derivatives under physiological conditions. Multiple spectroscopic and computational methods were employed to evaluate the binding interaction. The study found that both the quinoline derivatives bound with both BSA and HSA at site III (sub-domain IB) and quenched the fluorescence of the protein through a static quenching mechanism. The binding constant (Kb) at the level of 104 L mol-1 and the number of binding site was determined to be approximately: (1) the binding mode based on thermodynamic parameters (298,308, and 318 K) suggested a spontaneous process, indicating that the interaction could be hydrogen bonding and van der Waals force. Additionally, the molecular docking and molecular dynamics (MD) simulations corresponded with the spectroscopic results, confirming the binding interactions between the quinoline derivatives and both BSA and HSA. This research provides valuable insights for designing and developing quinoline derivatives to enhance their potency against HIV-1 RT inhibitors.

-