Interactions between Human Serum Albumin and Sulfadimethoxine Determined Using Spectroscopy and Molecular Docking

Abstract

Sulfonamides are widely used antibiotics in agricultural production. However, the potential threat of these drugs to human health has increased global concern. Human serum albumin (HSA) is the main reservoir and transporter of exogenous small molecules in humans. In this study, the interaction between sulfadimethoxine (SMT) and human serum albumin (HSA) was studied using spectroscopy and computer simulation. Our results showed that the hydrogen bonding and van der Waals forces drove SMT to enter the binding site I of HSA spontaneously and resulted in the fluorescence quenching of HSA. The stability of the HSA–SMT complex decreased with an increase in temperature. The binding of SMT to HSA induced alterations in the secondary structure of HSA, where the content of α-helix decreased from 61.0% of the free state to 59.0% of the compound state. The π–π, π–σ, and π–alkyl interactions between HSA and SMT were found to play important roles in maintaining the stability of the complex.

Multi‐Spectroscopic and Theoretical Analyses of Human Serum Albumin Binding to a Water‐Soluble Zinc(II) Complex including β‐Amino Alcohol

“…The negative values of both ▵H o and ▵S o confirm the involvement of hydrogen bonds and van der Waals forces in the HSA‐zinc(II) complex binding process [37] . These findings are consistent with the results reported in the literature for HSA binding to sulfadimethoxine, [34d] dicofol, [34a] and BSA binding to ZnSe QDs, [34b] also, HSA / BSA interaction with the complexes of zinc and iron [34c] . As well, HSA interaction with [Zn(bpy)(Gly)]NO 3/ [Zn(phen)(Gly)]NO 3 [38] and zinc(II) complexes synthesized from two types of Schiff base [6b,39] …”

“…The types of non‐covalent interactions including hydrogen bonds, van der Waals forces, hydrophobic, and electrostatic interactions have a fundamental contribution in ligand‐protein binding [36] . The thermodynamic analysis is a classical approach evaluating these interactions according to the theory proposed by Ross [34d] . The forces mentioned above are indicated by the symbol and quantity of varied thermodynamic constants, such as ΔH o (enthalpy change), ΔS o (entropy change), and ΔG o (Gibbs free energy change) [36] .…”

“…Two aromatic amino acid residues (tyrosine and tryptophan) exist in site I, whereas only tyrosine residue exists in site II. Small molecules bind to albumin protein mainly through these two binding sites [34a,d] . Therefore, the site marker replacement studies were accomplished utilizing site‐specific drugs (warfarin and ibuprofen) to detect the zinc(II) complex binding site to HSA [40] .…”

PI3K/mTOR Dual Inhibitor Pictilisib Stably Binds to Site I of Human Serum Albumin as Observed by Computer Simulation, Multispectroscopic, and Microscopic Studies

“…Steady-state fluorescence spectroscopy, a simple and convenient method, can judge the occurrence of ligand-protein interactions and further provide vital information, such as quenching mechanism, binding constant, number of binding sites, and thermodynamic data [9,10]. The effect of GDC-0941 on the fluorescence intensity of HSA at 298 K is shown in Figure 5A.…”

“…Human serum albumin (HSA) is a principal extracellular protein with a concentration of 40 mg•mL −1 or 0.6 mM in blood plasma and contains 50-60% of total plasma protein in humans [7,8]. Research showed that the distribution, free concentration, and metabolism of drugs can be considerably altered as a result of their binding to HSA [9][10][11]. If the affinity of the drug binding to HSA in the plasma is strong, the drug will be transported to the target tissue and cannot be dissociated from HSA.…”