Design, synthesis, and molecular modeling of heterodimer and inhibitors of α-amylase as hypoglycemic agents

A series of rosiglitazone-based heterodimers were designed and synthesized, and their a-amylase and antioxidant activity was evaluated. The binding mode of the compounds at the active site of PPAR gamma and alpha-amylase enzyme was explored using MolDock docking method. In molecular docking studies against crystal structure of PPAR gamma (PDB code: 1FM6), compounds 10 and 13 showed interaction with amino acids Arg379, Asp379, Asn385, Ala387, Glu388, Val389, Glu390, and Lys438. Docking results of alpha-amylase enzyme (PDB code: 5EOF) with compounds 10 and 13 showed excellent interaction with amino acids Ala169, Lys172, Asp173, Tyr174, Val175, Arg176, and Lys178. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. All synthesized compounds were subjected to in vitro alpha-amylase activity and antioxidant activity. Compounds 10 and 13 were to possess higher potency than acarbose, and most of the compounds showed antioxidant activity. Additionally, the most active compound 10 was evaluated for in vivo anti-diabetic activity. [GRAPHICS] .

Automated summary

A series of rosiglitazone-based compounds were designed and synthesized, and their biological activities were evaluated. The binding mode of these compounds with PPARγ and α-amylase was explored using molecular docking method. The results showed that compounds 10 and 13 exhibited potent anti-diabetic and antioxidant activities.