Studies of the Interaction between Isoimperatorin and Human Serum Albumin by Multispectroscopic Method: Identification of Possible Binding Site of the Compound Using Esterase Activity of the Protein

Abstract

Isoimperatorin is one of the main components of Prangos ferulacea as a linear furanocoumarin and used as anti-inflammatory, analgesic, antispasmodic, and anticancer drug. Human serum albumin (HSA) is a principal extracellular protein with a high concentration in blood plasma and carrier for many drugs to different molecular targets. Since the carrying of drug by HSA may affect on its structure and action, we decided to investigate the interaction between HSA and isoimperatorin using fluorescence and UV spectroscopy. Fluorescence data indicated that isoimperatorin quenches the intrinsic fluorescence of the HSA via a static mechanism and hydrophobic interaction play the major role in the drug binding. The binding average distance between isoimperatorin and Trp 214 of HSA was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity (PSH) was also documented upon isoimperatorin binding. Furthermore, the synchronous fluorescence spectra show that the microenvironment of the tryptophan residues does not have obvious changes. Site marker compettive and fluorescence experiments revealed that the binding of isoimperatorin to HSA occurred at or near site I. Finally, the binding details between isoimperatorin and HSA were further confirmed by molecular docking and esterase activity inhibition studies which revealed that drug was bound at subdomain IIA.

Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9

“…The amide I peak position occurs in the region 1600-1700 cm −1 and the amide II band 1500-1600cm −1 . Amide I band is more sensitive to the change of protein secondary structure than amide II [32,33]. Figure 2 shows the FT-IR spectrum of free MMP9 and the FT-IR spectra after binding with GBA.…”

Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin

“…During a fluorescence titration experiment at the wavelength of excitation or at the wavelengths used to follow an emission, the absorption of the molecule added resulted in a spurious decrease in the observed fluorescence intensity [11]. In the steady-state fluorescence experiments, absorption spectrum of drugs overlaps with the excitation and emission of proteins.…”

“…The binding of drugs to plasma proteins (especially albumin) affects their distribution and rate of metabolism [10]. Crystal structure analyses have revealed that HSA has two hydrophobic pockets as binding sites for aromatic and heterocyclic ligands; one site in subdomain IIA (commonly referred to as Sudlow's site I: warfarin-binding site) and the other within subdomain IIIA (commonly referred to as Sudlow's site II: indole/ benzodiazepine site) [11]. Both hydrophobic and electrostatic interactions play a major role in controlling the affinity towards drug binding for sites I and II; for site I, mainly hydrophobic interactions are dominant, whereas for site II, a combination of hydrophobic, hydrogen bonding, and electrostatic interactions all play a crucial role [11,12].…”

Binding of hydroxylated polybrominated diphenyl ethers with human serum albumin: Spectroscopic characterization and molecular modeling

“…In recent years, interactions among small molecules, drugs, and surfactants with proteins have been studied extensively, particularly the structural aspects, because it is important to elucidate the molecular aspects of binding to establish the structure–function relationship on the one hand and drug design and efficacy on the other hand . In particular, affinity, toxicity, and structural modifications of serum proteins have been studied to determine the efficacy of drug distribution in the target sites.…”