Structure -based Design and Computational Evaluation of Spiropyrrolidine Derivatives as Novel Acetylcholinesterase Inhibitors

A series of dispiro-acenaphthenone grafted dipyrrolopiperazine derivatives were synthesized via a 1,3-dipolar cycloaddition reaction and evaluated for their antimicrobial and antioxidant activities. The synthesized compounds were screened against clinically significant human pathogens, including Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus, using the agar well diffusion method. All compounds demonstrated moderate antibacterial activity, with compound 4b showing comparatively stronger inhibition and lower minimum inhibitory concentration (MIC) values against both Gram-positive and Gram-negative bacteria. Antioxidant potential was assessed through DPPH free radical scavenging assays and dot-blot screening. Among the tested derivatives, selected compounds exhibited notable radical scavenging activity with measurable IC₅₀ values, indicating their potential as antioxidant agents. The incorporation of the acenaphthenone moiety into spiropyrrolidine frameworks significantly enhanced the biological activity of the synthesized molecules. These findings suggest that dispiro-acenaphthenone grafted dipyrrolopiperazine derivatives may serve as promising candidates for the development of novel antimicrobial and antioxidant agents