Spectroscopic and molecular docking study on the structure–affinity relationship and mechanism in the interaction of genistein and its derivatives with bovine serum albumin

Abstract

In this paper, the interaction of genistein (GEN) and its four derivatives (GEN1-4) with bovine serum albumin (BSA) were investigated by ultraviolet-visible absorption spectra, fluorescence, synchronous fluorescence, three-dimensional fluorescence spectroscopy, circular dichroism and molecular docking techniques. The experimental results showed that the intrinsic fluorescence of BSA was quenched by genisteins and was due to the formation of a genisteins-BSA complex. The quenching constant, binding constants, binding sites, intermolecular distances and thermodynamic properties were calculated at 298 K, 306 K and 310 K. Site marker competitive experiments indicated that the binding site of genisteins to BSA was mainly located in subdomain IIA. The conformational investigation showed that the presence of 0020 genisteins led to changes in the secondary structure of BSA and induced the slight unfolding of protein polypeptides, which confirmed some micro-environmental and conformational changes of BSA molecules. Furthermore, the binding affinity decreased in the order GEN1 > GEN > GEN4 > GEN3 > GEN2, which revealed that different type and position of substituents of genistein significantly influenced the affinity of compounds to BSA. The number of hydroxyl groups on the ring A was the most important factor because increasing the hydroxyl groups on ring A clearly enhanced the binding affinity. However, trifluoromethylation did not much affect the affinity, alkylation, esterification and difluoromethylation slightly enhanced the binding affinity. The results obtained herein will provide valuable information about the pharmacokinetics at a molecular level and be a useful guideline for the further design of much more suitable genistein derivatives.

Synthesis of novel genistein amino acid derivatives and investigation on their interactions with bovine serum albumin by spectroscopy and molecular docking

“…Atomic charges of BSA were reckoned using Gasteiger–Huckel and AMBER7FF99 method. 14 Then the ‘protomol’ file of BSA was generated.…”

“… 10–12 In recent years, the interactions between chlorinated, 13 alkylated and trifluoromethylated genisteins and BSA were reported by several groups. 14 However, the studies on the structural affinity relationship between genistein amino acid derivatives and BSA have not yet been published.…”

Therapeutic Potential of Genistein and its Derivatives as a Target for Anticancer Agents

“…The binding affinity of genistein and its derivatives was found to be in order 20 > 1 > 21 > 22 > 23 (Figure 6). [140] …”

“…The binding affinity of genistein and its derivatives was found to be in order 20 > 1 > 21 > 22 > 23 (Figure 6). [140] Du et al studied the chemopreventive activity of compound 24 (Figure 7), a genistein derivative in collitis associated colorectal cancer. The compound inhibited the proliferation of cancer cells via inhibiting β-catenin activity.…”

Digital Database of Absorption Spectra of Diverse Flavonoids Enables Structural Comparisons and Quantitative Evaluations

“…Such mixtures may together be used as natural colorants. − (ii) The role of flavonoids in filtering incident UV-B radiation. (iii) The ability to filter ultraviolet radiation in sunscreen products from natural origin − and UV protective fabric/clothing. − (iv) Studies of flavonoids with proteins, enzymes, and albumins (e.g., bovine serum albumin, human serum albumin, casein, lactoglobulin, lipoproteins) by use of Förster (or fluorescence) resonance energy transfer (FRET) calculations. − <...…”