New 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: synthesis, in vitro and in silico enzymatic and toxicity evaluations

Fragment-Based Dynamic Combinatorial Chemistry for Identification of Selective α-Glucosidase Inhibitors

“…Indeed, acarbose, miglitol and voglibose are clinically prescribed α-amylase and α-glucosidase inhibitors for the treatment of T2DM. , However, serious side effects such as diarrhea, gastrointestinal distress, and abdominal distension are often reported during the application of those medicines. , Several enzymatic studies have documented that α-amylase inhibition is one of the leading causes for gastrointestinal side effects, as it can also facilitate the transfer of undigested polysaccharides to the intestine . Under such circumstances, selective inhibition of α-glucosidase can reduce the production of glucose on the one hand and circumvent the possible intestinal side effects of α-amylase inhibition on the other . Therefore, the development of efficient and selective α-glucosidase inhibitors is in great demand.…”

“…27 Under such circumstances, selective inhibition of α-glucosidase can reduce the production of glucose on the one hand and circumvent the possible intestinal side effects of α-amylase inhibition on the other. 28 Therefore, the development of efficient and selective α-glucosidase inhibitors is in great demand.…”

Identification of dual-target isoxazolidine-isatin hybrids with antidiabetic potential: Design, synthesis, in vitro and multiscale molecular modeling approaches

“…kinetic studies were carried out based on the above IC 50 values and the in vitro assays for the most potent inhibitor ( 5d ) and acarbose to determine their inhibition mode towards both enzymes. A volume of 20 μL was incubated for 15 min at 30 °C by using the varying concentration of the inhibitor 5d against α-amylase (0, 5, 15 and 33 μM) and α-glucosidase (0, 15, 40, and 65 mM) with varying concentrations of inhibitor substrate (starch) in the range 0.25–5 mM, whereas the concentrations for the inhibitor substrate ( p -nitrophenyl-α-D-glucopyranoside, P -NPg) were in the range 0.1–1.3 mM, respectively, according to some previously methods, with minor modification [ 83 , 84 ]. The type of inhibition of the enzyme was assessed by preparing Lineweaver-Burk plots of the inverse of the velocities (1/V) versus the inverse of the substrate's concentration 1/[S] mM −1 , and change in absorbance was measured spectrophotometrically at 405 nm.…”

Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives

“…The validated docking method was then used to analysis of the binding modes of the newly synthetized compounds 8a-p over the α-glucosidase active site in comparison to acarbose as a standard inhibitor of this enzyme. The reliability of the induced fit docking procedure was conducted according to our previous set up studies based on re-docking of α-d-glucose as the enzyme substrate 25,26 .…”