Shifting the paradigm of diabetes mellitus therapeutics: synthesis of novel fused pyrrolo-Imidazolidinone derivatives and their kinetic and computational profiling

Abstract

Diabetes mellitus remains a major global health challenge, necessitating the search for potent and safer therapeutic agents. In this study, a series of novel pyrrolo-imidazolidinone derivatives (1–10) was designed and synthesized as potential anti-diabetic agents. Structural elucidation was carried out using HREI-MS, ¹H-NMR and ¹³C-NMR spectroscopy. The anti-diabetic potential of the compounds was evaluated in vitro against α-amylase and α-glucosidase enzymes. Among the synthesized derivatives, compounds 4, 5, and 7 exhibited the most potent inhibitory activity, with IC₅₀ valuesranging between 4.10 ± 0.30 to 2.10 ± 0.10 µM (α-amylase) and 4.80 ± 0.40 to 2.60 ± 0.20 µM (α-glucosidase), surpassing the reference drug acarbose (IC₅₀ = 4.20 ± 0.60 µM and 5.10 ± 0.10 µM, respectively). In silico studies, including molecular docking, pharmacophore modeling, and ADMET profiling, supported the experimental findings and provided insights into the structural features governing enzyme inhibition and drug-likeness. The results highlight pyrrolo-imidazolidinone derivatives as promising scaffolds for further development of effective anti-glycemic agents.