Publications by authors named "Mitra Kiani"

2 Publications

  • Page 1 of 1

Novel Coumarin Containing Dithiocarbamate Derivatives as Potent α-Glucosidase Inhibitors for Management of Type 2 Diabetes.

Med Chem 2021 ;17(3):264-272

Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, Iran.

Background: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in 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 from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a 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 a standard inhibitor (IC50 = 750.0 ± 9.0 μM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket.

Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes.
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http://dx.doi.org/10.2174/1573406416666200826101205DOI Listing
January 2021

Biscoumarin-1,2,3-triazole hybrids as novel anti-diabetic agents: Design, synthesis, in vitro α-glucosidase inhibition, kinetic, and docking studies.

Bioorg Chem 2019 11 16;92:103206. Epub 2019 Aug 16.

Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran 1439955991, Iran. Electronic address:

A novel series of biscoumarin-1,2,3-triazole hybrids 6a-n was prepared and evaluated for α-glucosidase inhibitory potential. All fourteen derivatives exhibited excellent α-glucosidase inhibitory activity with IC values ranging between 13.0 ± 1.5 and 75.5 ± 7.0 µM when compared with the acarbose as standard inhibitor (IC = 750.0 ± 12.0 µM). Among the synthesized compounds, compounds 6c (IC = 13.0 ± 1.5 µM) and 6g (IC = 16.4 ± 1.7 µM) exhibited the highest inhibitory activity against α-glucosidase and were non-cytotoxic towards normal fibroblast cells. Kinetic study revealed that compound 6c inhibits the α-glucosidase in a competitive mode. Furthermore, molecular docking investigation was performed to find interaction modes of the biscoumarin-1,2,3-triazole derivatives.
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http://dx.doi.org/10.1016/j.bioorg.2019.103206DOI Listing
November 2019