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

• Published in: Molecular diversity 2023-02, Vol.27 (1), p.209-222
• Main Authors: Singh, Ved Prakash, Nidhar, Manisha, Yadav, Pratima, Kumar, Ranjeet, Sonker, Priyanka, Tewari, Ashish Kumar
• Format: Article
• Language: English
• Subjects: alpha-Amylases - chemistry; Amino acids; Antioxidants; Antioxidants - pharmacology; Biochemistry; Biomedical and Life Sciences; Enzymes; Hypoglycemia; Hypoglycemic Agents - chemistry; Life Sciences; Molecular Docking Simulation; Molecular Structure; Organic Chemistry; Original Article; Pharmacy; Polymer Sciences; PPAR gamma; Structure-Activity Relationship
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-022-10414-8

A series of rosiglitazone-based heterodimers were designed and synthesized, and their α-amylase and antioxidant activity was evaluated. The binding mode of the compounds at the active site of PPARγ and α-amylase enzyme was explored using MolDock docking method. In molecular docking studies against crystal structure of PPARγ (PDB code: 1FM6), compounds 10 and 13 showed interaction with amino acids Arg379, Asp379, Asn385, Ala387, Glu388, Val389, Glu390, and Lys438. Docking results of α-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 α-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. Graphical abstract