Spectroscopic and in silico evaluation on the interactive behavior between substituted β-2,3-dihydrofuran naphthoquinones and human serum albumin

Abstract

The interactive profile between human serum albumin (HSA, the main carrier of endogenous and exogenous compounds in the human bloodstream) and five potential anticandidal agents, namely 2,3-dihydro-2-phenyl-naphtho[1,2-b]furan-4,5‑dione (1) and its derivatives 2–5 was studied by biophysical techniques, i.e., UV–vis, circular dichroism, steady-state and time-resolved fluorescence, combined with in silico calculations. The Stern-Volmer quenching constant (KSV) trend in three different temperatures and the bimolecular quenching rate constant (kq ≈ 1012 M−1s−1) values indicated a ground-state association HSA:1–5 which was confirmed by time-resolved fluorescence decays. Both KSV and modified Stern-Volmer binding constant (Ka) values are in the order of 104 M−1, indicating a moderate binding affinity, following the same reported trend for 1,4-naphthoquinones (the isomeric form of the naphthoquinones under study). There is only one main binding site for HSA:1–5, probably the subdomain IIA where the Trp-214 residue can be found. The association is driven both enthalpically and entropically, perturbing both the microenvironment around Trp-214 residue and weakly the α-helix content of albumin. Overall, the β-2,3-dihydrofuran naphthoquinones 1–5 showed favorable binding affinity to HSA to achieve their therapeutical potential and control of effective dosages.

Keywords

• HSA-binding
• Naphthoquinones
• Biophysical approach
• Pharmacokinetic