Synthesis and bioactivities evaluation of quinazolin-4(3H)-one derivatives as α-glucosidase inhibitors

Abstract

The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a–r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus.

Identification of bioactive compounds from the ethnomedicinal plant Senna alata (L.) Roxb. (fabaceae) through in vitro and molecular docking analysis against ?-glucosidase enzyme: a diabetic drug target

“…The docking analysis scores for the selected ligands indicated that the ligand was able to attach to a target protein pocket. These selected ligands have a binding affinity of less than -6.50 kcal/mol, which can be considered to be a good inhibitor of enzymatic reactions (40). In the present study, among nine plant derived compounds, 5 natural compounds revealed a binding affinity value greater than -6.5 kcal/mol with 5NN8.…”

Prevalence of Hyperlipidemia in Newly Diagnosed and Uncontrolled Type-2 Diabetes Mellitus Patients Comparative to Non-diabetic Individuals

“…(66) Quinazolin-4(3H)-one derivatives have also been evaluated for their inhibitory effects on TXNIP and have shown potential as αglucosidase inhibitors, which could improve the metabolic status of diabetic patients by modulating lipid metabolism. (67,68,69) However, there were some limitations in our study which should be taken into consideration. The study only included 83 participants, which may not be representative of the entire population of patients with type-2 diabetes mellitus in this district of Bangladesh.…”

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

“…The mode of inhibition of the most active compounds 6l and 6m identified with the lowest IC 50 , was investigated against an α-glucosidase activity with different concentrations of p -nitrophenyl α - d -glucopyranoside (1–12 mM) as substrate in the absence and presence of 6l and 6m at different concentrations. A Lineweaver–Burk plot was generated to identify the type of inhibition and the Michaelis–Menten constant ( K m ) value was determined from the plot between the reciprocal of the substrate concentration (1/[S]) and reciprocal of enzyme rate (1/V) over various inhibitors concentrations 30 , 31 .…”