Background:
α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and
starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus.
Objective:
In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated
against α-glucosidase in vitro and in silico.
Methods:
These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon
disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In
vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the
most potent compounds was also performed by Auto Dock Tools (version 1.5.6).
Results:
Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0
± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary
amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site
pocket.
Conclusion:
Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.
ZnS-Ag 2 S core-shell nano/hetero-junctions have been synthesized by a two-step co-precipitation technique, in which thin layers of Ag 2 S have been successfully coated on the surface of ZnS nanospheres. Structural studies and elemental analysis have been performed using X-ray diffraction, Fourier transfer infrared spectroscopy, field emission scanning electron microscopy, energy dispersive spectroscopy, and high-resolution transmission electron microscopy. UV-Vis diffuse reflectance spectroscopy and photoluminescence spectroscopy have been employed to investigate linear optical characteristics. Nanosecond laser pulsed-based single-beam Z-scan analysis has been used to examine the magnitude and the sign of the third-order nonlinear refractive indices. Samples show negative values of nonlinear refractive indices indicating self-defocusing optical nonlinearity under 1064 nm excitation. The results have shown that the third-order nonlinear refractive index in ZnS nanospheres can reach the magnitude of 61.0 × 10 −12 m 2 ∕W by encapsulating such a nanostructure within nanometer shells of Ag 2 S. The enhanced nonlinearity for ZnS-Ag 2 S core-shells has been found to be 9 times higher than sole ZnS nanoparticles, which was estimated to be about 6.4 × 10 −12 m 2 ∕W.
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