Molecular interaction of posaconazole with human serum albumin: a spectroscopic and computational approach

Abstract

Understanding drug–protein interactions is essential for optimizing pharmacokinetic properties and therapeutic efficacy. In this study, the binding mechanism of the antifungal drug posaconazole (PZA) with human serum albumin (HSA) was systematically investigated using a combination of spectroscopic techniques and molecular docking. UV–visible spectroscopy indicated complex formation, as evidenced by a hyperchromic shift upon HSA addition. Fluorescence quenching studies revealed significant interaction between PZA and HSA, with binding and quenching constants in the range of 10⁴ M⁻¹. Thermodynamic parameters (ΔH° = 2.676 kJ mol⁻¹; ΔS° = −19.30 J mol⁻¹ K⁻¹) suggest that the binding process is primarily driven by hydrophobic forces, van der Waals interactions, and electrostatic attractions. Molecular docking analysis further confirmed the spontaneous binding of PZA at a site between subdomains IIA and IIB of HSA, located between the classical binding sites I and II. Circular dichroism (CD) spectroscopy showed that the secondary structure of HSA remained largely unaltered upon drug binding, indicating minimal conformational change. These findings provide valuable insights into the molecular basis of PZA–HSA interactions, with implications for drug design and delivery.