Abstract
In the present work, we have examined the binding parameters, thermodynamics, and stability of human serum albumin (HSA) isoforms at pH 7.4 and 9.0, using spectroscopic, calorimetric, and molecular docking methods in the presence of water-soluble camptothecin analog irinotecan hydrochloride (CPT-11). We observed that CPT-11 binds to HSA through a static quenching procedure of ground-state complex formation with N-isoform and B-isoform. Hydrogen bond and hydrophobic interactions are the major governing forces that participating in the formation of protein-drug complex. To determine the binding site of CPT-11 within HSA molecules, we also have performed molecular docking experiments. We explored the CPT-11-mediated stability and modulation of HSA by performing dynamic light scattering (DLS) and differential scanning calorimetry (DSC) experiments. DLS and DSC techniques are used to determine the size and the melting point (T-m) of HSA, which was decreased in the presence of CPT-11. Therefore, CPT-11 plays an important role in HSA stability and protein-ligand interactions. The present study provides valuable information in the field of pharmacokinetics, pharmaco-dynamics, and drug discovery.