Spectroscopic analysis on structure–affinity relationship in the interactions of different oleanane‐type triterpenoids with bovine serum albumin

Abstract

Oleanane-type triterpenoids serve as an important group of plant secondary metabolites with a variety of biological activities and the C-3 position substitution pattern is a significant structural feature for their biological activities. Three selected oleanane-type triterpenoids (glycyrrhizin, glycyrrhetinic acid, and carbenoxolone) bearing different substituents (glucuronic acid dimer, hydroxyl, and succinyl groups) at the C-3 position were studied for their affinities to bind bovine serum albumin (BSA) by steady-state fluorescence, synchronous, three-dimensional fluorescence and ultraviolet-visible (UV-vis) absorption spectra. The binding mechanism of the triterpenoids to BSA is due to the formation of the triterpenoids-BSA complex and the binding affinity is strongest for carbenoxolone and ranked in the order carbenoxolone > glycyrrhetinic acid > glycyrrhizin. The thermodynamic parameters calculated at different temperatures showed that triterpenoids binding to BSA primarily depended on hydrophobic interaction and hydrogen bonding. The distance between the bound triterpenoid and BSA was determined on the basis of the Förster's energy transfer theory. Displacement experiments using phenylbutazone and ibuprofen showed the binding site of triterpenoids on BSA at subdomain IIA (Sudlow's site I). The effect of triterpenoids on BSA conformation was analyzed by UV-vis absorption, and synchronous and three-dimensional fluorescence spectra. These results revealed that the C-3 position substitution pattern significantly affects the structure-affinity relationships of oleanane-type triterpenoid binding to BSA and further affects the bioavailability of triterpenoids in the blood circulatory system.

A drug library screen identifies Carbenoxolone as novel FOXO inhibitor that overcomes FOXO3-mediated chemoprotection in high-stage neuroblastoma

“…As shown by EMSA ( Fig. 2d), the relatively high concentrations of CBX are needed due to binding to BSA, which is in concordance with the literature [37]. Importantly, CBX is rapidly absorbed in vivo following oral administration of an aqueous solution of the sodium salt to patients and attains high blood plasma concentrations of up to 175 µM without severe side effects [65] this exceeds the concentration at which we observed FOXO3 inhibition, suggesting its potential clinical application.…”

“…2c). This discrepancy is likely due to binding of CBX to albumin in the used cell culture media [37]. Using media with reduced amounts of fetal calf serum (medium supplemented with 0.1% FCS), 80 µM CBX were sufficient to halve the signal (Fig.…”

Explication of bovine serum albumin binding with naphthyl hydroxamic acids using a multispectroscopic and molecular docking approach along with its antioxidant activity

“…The force acting between biomolecules and small molecular ligands could be any non‐covalent force including hydrogen bonds, van der Waals’ forces, hydrophobic forces and electrostatic interactions . To determine the type of force existing during the HAs–BSA interaction, temperature‐dependent experiments were performed.…”

Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids

“…When HSA or glycated HSA samples were titrated with different amounts of flavonoids, the fluorescence spectrum of mixture was recorded from 295nm to 420 nm using a fluorometer (Hitachi F-7000, Tokyo, Japan) upon excitation wavelength at 280 nm. The fluorescence quenchings of HSA and glycated HSA with samples were calculated by Stern-Volmer formula shown as follow [19]:…”