Rational Design of New Quinoline-Benzimidazole Scaffold Bearing Piperazine Acetamide Derivatives As Antidiabetic Agents Publisher Pubmed



Ghasemi M¹ ; Iraji A^{2, 3} ; Dehghan M⁴ ; Lotfi Nosood Y¹ ; Irajie C⁵ ; Bagherian Khouzani N⁶ ; Mojtabavi S⁷ ; Faramarzi MA⁷ ; Mahdavi M⁸ ; Alharrasi A¹ Show Affiliations
Source: Bioorganic Chemistry Published:2024

Abstract

In this study, a series of fifteen compounds (7a–o) based on a quinoline-benzimidazole scaffold bearing piperazine acetamide derivatives were synthesized and evaluated for their potential as α-glucosidase inhibitors, which are important therapeutic agents in the management of type 2 diabetes mellitus. Among the synthesized compounds, 7m exhibited the most potent inhibitory activity, demonstrating a 28-fold greater efficacy than the standard clinical inhibitor, acarbose. Molecular docking studies indicated strong binding interactions between 7m and the α-glucosidase active site, including hydrogen bonding, π–π stacking, and π-cation interactions. Furthermore, molecular dynamics simulations revealed that compound 7m formed a highly stable complex with the enzyme. These findings suggest that compound 7m is a promising candidate for further development as an effective antidiabetic agent, offering valuable insights into the design of potent α-glucosidase inhibitors based on the quinoline-benzimidazole framework. © 2024 Elsevier Inc.