Synthesis and Molecular Docking Studies of New Aryl Imeglimin Derivatives As a Potent Antidiabetic Agent in a Diabetic Zebrafish Model Publisher Pubmed



Khodakhah A¹ ; Mohammadi H² ; Abdoli S¹ ; Zarei I¹ ; Palimi M¹ ; Ekhtiari Z¹ ; Talebi M¹ ; Biglar M³ ; Khorramizadeh MR² ; Amanlou M^{1, 3, 4}
Source: Scientific Reports Published:2024

Abstract

Diabetes mellitus (DM) is a persistent, progressive, and multifaceted disease characterized by elevated blood glucose levels. Type 2 diabetes mellitus is associated with a relative deficit in insulin mainly due to beta cell dysfunction and peripheral insulin resistance. Metformin has been widely prescribed as a primary treatment option to address this condition. On the other hand, an emerging glucose-reducing agent known as imeglimin has garnered attention due to its similarity to metformin in terms of chemical structure. In this study, an innovative series of imeglimin derivatives, labeled 3(a–j), were synthesized through a one-step reaction involving an aldehyde and metformin. The chemical structures of these derivatives were thoroughly characterized using ESI–MS, 1H, and 13C NMR spectroscopy. In vivo tests on a zebrafish diabetic model were used to evaluate the efficacy of the synthesized compounds. All compounds 3(a–j) showed significant antidiabetic effects. It is worth mentioning that compounds 3b (FBS = 72.3 ± 7.2 mg/dL) and 3g (FBS = 72.7 ± 4.3 mg/dL) have antidiabetic effects comparable to those of the standard drugs metformin (FBS = 74.0 ± 5.1 mg/dL) and imeglimin (82.3 ± 5.2 mg/dL). In addition, a docking study was performed to predict the possible interactions between the synthesized compounds and both SIRT1 and GSK-3β targets. The docking results were in good agreement with the experimental assay results. © The Author(s) 2024.