Hybrids of Isatin‐Pyrazole as Potential α‐Glucosidase Inhibitors: Synthesis, Biological Evaluations and Molecular Docking Studies

Abstract

α‐Glucosidase inhibition has been considered as an effective strategy for controlling the post‐prandial hyperglycemia in diabetic patients. A series of novel isatin‐pyrazole hybrids has been rationally designed, synthesized and characterized by different spectroscopic techniques. All of the synthesized compounds were evaluated for their α‐glucosidase inhibitory potential using in vitro enzymatic assay. The tested compounds have exhibited potent α‐glucosidase inhibition with IC50 values ranging from 3.26±0.25 to 32.33±1.08 μM. Compound V7, having 3‐nitro phenyl ring appended at pyrazole nucleus, has emerged as the most potent inhibitor among the series with an IC50 value of 3.26±0.25 μM, which was approximately 146 fold more potent than the clinically used drug acarbose (IC50=478.07±1.53 μM). Molecular docking studies were carried out to investigate the binding interactions of most active compounds with the active site of the enzyme. Further, in silico predictive pharmacokinetic parameters (ADME) and drug‐like properties of the compounds were within the acceptable ranges. In vivo biological evaluations further supplemented the in vitro results.

Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

“…Appropriately in silico pharmacokinetic properties for hybrids with enhanced α-glucosidase inhibitory activity could catalyze future production and development of physiologically active α-glucosidase inhibitors. [70] A series of novel antidiabetic drugs containing via pyrazolylthiazolidin-4-one pharmacophore has been designed and containing methoxy groups on the phenyl ring and nitro groups on the pyrazole ring that were coupled to thiazolidine-4-one had the highest total (e.s.u) value. High second-order nonlinear optical characteristics are related with substances replaced with electronwithdrawing groups on one side and electron-releasing groups on another side.…”

Recent Advances in Synthesis and Properties of Pyrazoles

“…Similarly, Kaur et al [36] synthesized 4-formyl-1-phenylpyrazoles 31a-f using the Vilsmeier-Haack reaction with phenylhydrazones 30a-f, POCl 3 , and DMF. The corresponding substrates 30a-f were obtained by a condensation reaction between phenylhydrazine (9a) and acetophenones 24a-f in ethanol using acetic acid as a catalyst (Scheme 7a).…”

Trithiazacrown Ethers Containing Piperidine Heterocycle: Synthesis, Structural Characterization and Evaluation Of α‐Glucosidase Inhibitory Activity

“…However, acarbose and voglibose are expensive and have some side effects such as flatulence or abdominal bloating [2,3] . Therefore, the development of new α‐glucosidase inhibitors from both natural and synthetic sources is always necessary [4–11] . Like crown ether, thiacrown ether can be used selectively for metal ions in solution.…”

“…[2,3] Therefore, the development of new α-glucosidase inhibitors from both natural and synthetic sources is always necessary. [4][5][6][7][8][9][10][11] Like crown ether, thiacrown ether can be used selectively for metal ions in solution. However, in comparison with crown ethers, studies about thiacrown ether derivatives are still limited.…”