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 Publisher



Moghaddam FM ; Fazli H ; Sadredini S ; Hosseinzadeh N ; Mojtabavi S ; Faramarzi MA ; Foroumadi A
Source: Journal of Ionic Liquids Published:2026

Abstract

A new series of spiroacenaphthylene 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 min. 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 spiroacenaphthylene 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. © 2026 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/