Search

[Display omitted] • A novel 4-MPBA-MoS 2 QDs was synthesized by one-pot hydrothermal approach. • The prepared QDs have a uniform spherical appearance with a diameter of 1.5 ∼ 3.0 nm. • Inhibitory effects of the QDs on BSA amyloid aggregation were investigated. • Molecular docking reveals the mechanism of QDs inhibiting BSA amyloid aggregation. In recent years, seeking and screening of compounds that can inhibit and/or depolymerize protein aggregation has been a hot issue in the field of pharmaceutical research. As a new material, quantum dots have been widely concerned by medical researchers. In present study, a novel 4-mercaptophenylboronic acid functionalized MoS 2 quantum dots (4-MPBA-MoS 2 QDs) was successfully synthesized through a one-pot hydrothermal approach by using molybdate dehydrate and 4-mercaptophenylboronic acid as Mo and S source, respectively. Transmission electron microscopy observation showed that the morphology and microstructure of the 4-MPBA-MoS 2 QDs displayed uniform spherical shape with a diameter of approximately 1.5 ∼ 3.0 nm. The UV and fluorescence spectra experiments indicated that the prepared QDs had good water solubility and two weak absorption peaks were appeared at 280 nm and 310 nm. When the excitation wavelength was set to 310 nm, the 4-MPBA-MoS 2 QDs had the strongest fluorescence intensity, and the maximum emission wavelength appeared at 405 nm. In vitro experiments showed that the 4-MPBA-MoS 2 QDs could significantly reduce the aggregation of bovine serum albumin (BSA). Especially when the mass ratio of BSA to 4-MPBA-MoS 2 QDs was 1:5, the inhibition rate could reach 76.4%. Cell experiment showed that the presence of 4-MPBA-MoS 2 QDs could obviously decrease the cytotoxicity induced by BSA amyloid fibrils. Moreover, the depolymerization of BSA amyloid fibrils by 4-MPBA-MoS 2 QDs and its excellent cell permeability were also observed. Molecular docking studies have shown that 4-MPBA-MoS 2 QDs may stabilize the BSA structure through van der Waals forces, hydrophobic force, electrostatic interactions and hydrogen bonds formed between the outer layer of 4-MPBA and BSA to prevent fibrosis aggregation. The results of this study suggested that 4-MPBA-MoS 2 QDs showed low cytotoxicity, good biocompatibility and solubility, and had a great potential in the design of new drugs for the treatment of amyloid-related diseases. [ABSTRACT FROM AUTHOR]

In this work, the inhibitory effect of two isoflavonoids including daidzein and genistein on trypsin and their binding mechanism were determined by spectroscopic and molecular docking approaches. The results indicated that both daidzein and genistein reversibly inhibited trypsin in a competitive manner with IC 50 values of 68.01 × 10 −6 mol L −1 and 64.70 × 10 −6 mol L −1 and K i values of 62.12 × 10 −6 mol L −1 and 59.83 × 10 −6 mol L −1 , respectively. They could spontaneously bind with trypsin mainly through hydrophobic force and electrostatic interactions with a single binding site. Analysis of circular dichrosim spectra and molecular docking revealed that both isoflavonoids bound directly into the catalytic cavity and the microenvironment and secondary structure of trypsin were changed in this process, which caused the inhibition of trypsin activity. All these experimental results and theoretical data in this work would be help in understanding the mechanism of inhibitory effects of daidzein and genistein against trypsin and the potential of isoflavonoid to relieve symptoms of pancreatitis. [ABSTRACT FROM AUTHOR]

In the work described on this paper, the inhibitory effect of 10 flavonoids on pepsin and the interactions between them were investigated by a combination of spectroscopic and molecular docking methods. The results indicated that all flavonoids could bind with pepsin to form flavonoid–pepsin complexes. The binding parameters obtained from the data at different temperatures revealed that flavonoids could spontaneously interact with pepsin mainly through electrostatic forces and hydrophobic interactions with one binding site. According to synchronous and three-dimensional fluorescence spectra and molecular docking results, all flavonoids bound directly into the enzyme cavity site and the binding influenced the microenvironment and conformation of the pepsin activity site which resulted in the reduced enzyme activity. The present study provides direct evidence at a molecular level to understand the mechanism of digestion caused by flavonoids. [ABSTRACT FROM AUTHOR]

In the work described on this paper, the interactions between eight flavonoids and hyaluronidase (HAase), an important enzyme involved in a promoting inflammation pathway, were investigated by spectroscopic and molecular modeling methods. The results revealed that all flavonoids could interact with HAase to form flavonoid-HAase complexes. The binding parameters obtained from the data at different temperatures indicated that flavonoids could spontaneously bind with HAase mainly through electrostatic forces and hydrophobic interactions with one binding site. According to synchronous and three-dimensional fluorescence spectra and the molecular docking results, all flavonoids bound directly into the enzyme cavity site and the binding of flavonoid into the enzyme cavity influenced the microenvironment of the HAase activity site which led to the reduced enzyme activity. The present study provides direct evidence at a molecular level to understand the mechanism of inhibitory effect of flavonoid against HAase and explain the anti-inflammatory mechanism of the Traditional Chinese Medicines as anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

In the work described on this paper, the bindings of baicalein and chrysin with hyaluronidase (HAase) were studied by fluorescence, synchronous fluorescence, three-dimensional fluorescence and molecular docking methods. The results indicated that both of flavones could interact with HAase to form flavone–HAase complexes. The binding constant, number of binding sites and thermodynamic parameters were measured at different temperature, which indicated that flavones could spontaneously bind with HAase through electrostatic forces with one binding site. Based on synchronous and three-dimensional fluorescence spectra and the molecular docking results, both of flavones bound directly into the enzyme cavity site and the binding of flavones into the enzyme cavity influenced the microenvironment of the HAase activity site which resulted in the reduced HAase activity. The present study provides direct evidence at a molecular level to understand the mechanism of inhibitory effect of flavone against HAase and explain the anti-inflammatory mechanism of Scutellaria baicalensis Georgi as an anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

In this study, the binding mode of nobiletin (NOB) with pepsin was investigated by spectroscopic and molecular docking methods. NOB can interact with pepsin to form a NOB-pepsin complex. The binding constant, number of binding sites and thermodynamic parameters were measured, which indicated that NOB could spontaneously bind with pepsin through hydrophobic and electrostatic forces with one binding site. Molecular docking results revealed that NOB bound into the pepsin cavity. Synchronous and three-dimensional fluorescence spectra results provide data concerning conformational and some micro-environmental changes of pepsin. Furthermore, the binding of NOB can inhibit pepsin activity in vitro. The present study provides direct evidence at a molecular level to show that NOB could induce changes in the enzyme pepsin structure and function. [ABSTRACT FROM AUTHOR]

Highlights: [•] The interaction between silybin and pepsin was investigated by spectral and docking methods. [•] The hydrophobic interaction was the main mode for stabilizing the silybin-pepsin complex. [•] Synchronous and three-dimensional fluorescence spectra of silybin-pepsin were showed in paper. [•] The interaction of pepsin with silybin occurred in the hydrophobic cavity of pepsin. [•] The effect of silybin on pepsin activity was first investigated in rats. [ABSTRACT FROM AUTHOR]

The binding mode between tyrosinase and resveratrol/oxyresveratrol. (a) Overlapping map of the binging site with the lowest binding energy between tyrosinase and resveratrol/oxyresveratrol; (b) the binding of kojic acid with the amino acid residues in the active site; (c) the binding of resveratrol with the amino acid residues in the active site; (d) the binding of oxyresveratrol with the amino acid residues in the active site. The purple carets show the amino acid residues which involved in hydrogen bonding and electrostatic interaction, while the green carets indicate the amino acid residues which involved in van der Waals interaction. The broken display hydrogen bond and the direction of the arrow is from the donor to the acceptor. • The inhibitory effects of resveratrol/oxyresveratrol on tyrosinase were investigated. • The differences of inhibitory mechanism of them were revealed. • The inhibition mechanism was further verified by molecular docking. Resveratrol and oxyresveratrol are two natural polyhydroxy trans -stilbene products. Previous studies have shown that both of them can effectively inhibit the activity of tyrosinase. However, little attention has been paid to study the difference of their inhibitory mechanism. To reveal this difference, in this work a comparative study on the inhibitory effects of resveratrol and oxyresveratrol against cellular tyrosinase activity and melanin content were investigated by B16F0 cells, and the inhibitory mechanism of them on tyrosinase was revealed by cell-free tyrosinase inhibition, intrinsic fluorescence spectrum, circular dichroism and molecular docking. The results showed that the inhibitory capacity of oxyresveratrol toward tyrosinase activity and melanin formation was better than that of resveratrol. The difference of their inhibitory mechanism may be closely related to the different types of inhibition, the different strength of their interaction with tyrosinase and the different number of hydrogen bonds between them. The data in this study provide a scientific basis for revealing the inhibitory mechanisms of resveratrol and oxyresveratrol toward tyrosinase, and lay an experimental foundation for further development and utilization of them. [ABSTRACT FROM AUTHOR]