Synthesis of spiro acenaphthylene pyrrolizidine and pyrrolidine compounds via 1,3-dipolar cycloaddition in ionic liquid and the investigation of their biological activity as potent α-glucosidase inhibitors

A new series of spiro-acenaphthylene pyrrolizidine and pyrrolidine derivatives was synthesized via 1,3-dipolar cycloaddition of acenaphthoquinone with sarcosine or L-proline and various chalcone derivatives in the ionic liquid [Bmim]Br under ultrasonic irradiation at room temperature, with yields of up to 98% within 30 minutes. All compounds were fully characterized and evaluated for their α-glucosidase inhibitory activity. Most derivatives showed inhibitory activity, with IC₅₀ values ranging from 32.0 ± 0.3 to 463.4 ± 1.2 µM, showing lower IC₅₀ values than acarbose (IC₅₀ = 750.0 ± 1.5 µM). Notably, compound 4k, bearing a 4-nitro substituent, had the lowest IC₅₀ value (32.0 ± 0.3 µM), suggesting favorable interactions with the enzyme active site. These findings highlight the relevance of spiro-acenaphthylene scaffolds as non-glycosidic α-glucosidase inhibitors and demonstrate the utility of ionic liquids for rapid and sustainable heterocyclic synthesis, which may provide a basis for future in vivo and pharmacokinetic studies.