Exploring the Dual Inhibitory Activity of Novel Anthranilic Acid Derivatives towards α-Glucosidase and Glycogen Phosphorylase Antidiabetic Targets: Design, In Vitro Enzyme Assay, and Docking Studies

Abstract

A few new anthranilate diamide derivatives, 3a–e, 5a–c and 7a–d, were designed, synthesized, and evaluated for their inhibitory activity against two interesting antidiabetic targets, α-glucosidase and glycogen phosphorylase enzymes. Different instrumental analytical tools were applied in identification and conformation of their structures like; 13C NMR, 1H NMR and elemental analysis. The screening of the novel compounds showed potent inhibitory activity with nanomolar concentration values. The most active compounds (5c) and (7b) showed the highest inhibitory activity against α-glucosidase and glycogen phosphorylase enzymes IC50 = 0.01247 ± 0.01 µM and IC50 = 0.01372 ± 0.03 µM, respectively. In addition, in vivo testing of the highly potent α-glucosidase inhibitor (7b) on rats with DTZ-induced diabetes was done and showed significant reduction of blood glucose levels compared to the reference drug. Furthermore, a molecular docking study was performed to help understand the binding interactions of the most active analogs with these two enzymes. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. These data showed considerable antidiabetic activity for these newly synthesized compounds.

A Comparative Study of Anti-inflammatory Activity of Tecoma stans, Acalypha indica and Abutilon indicum Plant Leaf Extract

“…Leaves of Tecoma stans contain alkaloids, tecomine and tecostamine, which are potential hypoglycemic agents when provided intravenously [33,35]. Anthranilic acid is responsible for the antidiabetic activity of this plant and their roots are powerful diuretic and vermifuge [36]. The plant leaf extract of Acalypha indica also demonstrated antiinflammatory effect in a dose-dependent manner.…”

Medicinal chemistry of anthranilic acid derivatives: A mini review

“…The test compounds containing N‐ pyridyl nucleus exhibited a potent antidiabetic activity by significantly lowering the abnormal blood glucose level. The molecular docking analysis of test compounds for appraising their interactions with the active site residues of the target enzymes further validated their antidiabetic efficacy (Ihmaid, 2018).…”

An Anthranilate Derivative Inhibits Glutamate Release and Glutamate Excitotoxicity in Rats

“…Anthranilate derivatives have gained much attention in the area of drug discovery and development because of their diverse pharmacological activities, including anti-inflammatory, antiviral, immunosuppressive, anticancer, antithrombotic, antidiabetic, and analgesic activities [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Anthranilate derivatives were also reported to have antidepressant and anticonvulsant effects in different animal models [ 14 , 15 ], indicating that they are potential candidates for drug therapy for related diseases such as anxiety, depression, and epilepsy.…”