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Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with ?-glucosidase.
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ABSTRACT: Purpose
One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through ?-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postprandial hyperglycemia impaired the endogenous antioxidant defense due to inducing oxidative stress induced pancreatic ?-cell destruction through uncontrolled free radicals generation such as ROS, which in turn, leads to various macrovascular and microvascular complications. This study aimed to synthesize 2-aryl-4,6-diarylpyrimidine derivatives, screen their ?-glucosidase inhibitory activity, perform kinetic and molecular docking studies.Methods
A series of 3,4,5-triphenyl-4,5-dihydro-1,2,4-oxadiazole derivatives were synthesized and their ?-glucosidase inhibitory activity was screened in vitro. Compounds 6a-k were synthesized via a two-step reaction with a yield between 65 and 88%. The structural elucidation of the synthesized derivatives was performed by different spectroscopic techniques. ?-Glucosidase inhibitory activity of the oxadiazole derivatives 6a-k was evaluated against Saccharomyces cerevisiae ?-glucosidase.Results
Most of the synthesized compounds demonstrated ?-glucosidase inhibitory action. Particularly compounds 6c, 6d and 6 k were the most active compounds with IC50 values 215?±?3, 256?±?3, and 295?±?4 ?M respectively. A kinetic study performed for compound 6c revealed that the compound is a competitive inhibitor of Saccharomyces cerevisiae ?-glucosidase with Ki of 122 ?M. The docking study also revealed that the two compounds, 6c and 6 k, have important binding interactions with the enzyme active site.Conclusion
The overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel ?-glucosidase inhibitors to manage the postprandial hyperglycemia incidence. Graphical abstract.
SUBMITTER: Khosravi A
PROVIDER: S-EPMC7214590 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with α-glucosidase.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20200106 1
<h4>Purpose</h4>One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postprandial hyperglycemia impaired the endogenous antioxidant defense due to inducing oxidative stress induced pancreatic β-cell destruction through uncontrolled free radicals generation such as ROS, which in turn, leads to various macrovascular ...[more]