EC Pharmacology And Toxicology

<Aim: The aim of the study was to develop new anti-diabetic agents from synthetic route.

Materials and Methods: An attempt was made to synthesize various flavones. The structures of the compounds were elucidated by UV, IR, ¹H-NMR, and mass spectrometry. Furthermore, an in silico library of synthesized compounds were designed. Aldose reductase, protein tyrosine phosphate and alpha amylase were selected as targets to conducting in-vivo study to afford potential inhibition of those enzymes. Designed library of flavones were docked into the active site of all three enzymes and the most active 10 flavones (-9.71 to -6.72 kcal/mole) were selected for synthesis. Finally, selected compounds were evaluated for their in-vivo anti-diabetic activity by streptozotocin induced model.

Results: Docking study revealed that flavones such as F1, F2, F3, F5 and F8 were potentially considered for in-vivo anti-diabetic activity by streptozotocin induced model. Fasting blood glucose and biochemical parameters like total protein, urea, creatinine, SGOT, SALP and SGPT were performed for the biological evaluation and compared with that of standard glibenclamide (5 mg/kg). Among the five consolidated flavones, F8 possess high significant (p < 0.01) results and restores the blood glucose level, liver enzymes and renal parameters. Based on these results, a promising potent drug would be developed in the management of diabetes mellitus.

Conclusion: In-vivo evaluations of selected compounds were carried out for its anti-diabetic activity using three enzymes as a target. All the selected flavones showed excellent interactions with targeted enzymes and established a noticeable correlation between in silico score and in-vivo anti-diabetic activity.

 Keywords: Anti-Diabetic Activity; Aldose Reductase (AR); Protein Tyrosine Phosphatase 1B; Alpha Amylase; Streptozotocin; In Silico Score; Docking Study

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