Synthesis of N-Methylspiropyrrolidine Hybrids for Their Structural Characterization, Biological and Molecular Docking Studies

Abstract

A set of novel N-methylspiropyrrolidine hybrids have been synthesized regio selectively employing 1,3-dipolar cycloaddition reaction of substituted chalcones with azomethine ylides (work up in situ from isatin and sarcosine). The spiropyrrolidines structures were studied using FT-IR, ¹H and ¹³C NMR spectroscopic data, and was finally confirmed by X-ray diffraction study. Hirshfeld surface analysis was correlated with X-ray diffraction and described different intermolecular contacts. Good antibacterial activity was reported against gram-positive and gram-negative bacterial strains of Bacillus subtillis, Enterococcus faecalis, E. coli, and Pseudomonas aeruginosa. Initially, antibacterial activity of compounds was confirmed by the zone of inhibition. Most of the compounds have shown MIC and MBC in the range between 50-200 µg∕mL against both types of bacteria. Further, for mechanism of action, the tested compounds were checked for the inhibition of an established bacterial drug target, DNA gyrase using in silico approaches.

Keywords:

• N-Methylspiropyrrolidines
• azomethine ylide
• single crystal X-ray
• Hirshfeld surface analysis
• antimicrobial activity
• molecular docking study

Acknowledgments

This Project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. G: 237-130-1441. The authors, therefore, acknowledge with thanks DSR for technical and financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.