Phenyl substituted 3-chloro 2-azetidinones: Design, green synthesis, antimicrobial activity, and molecular docking studies

Abstract

In the present study, by applying an effective microwave-assisted synthesis method for some new phenyl substituted 3-chloro 2-azetidinone derivatives, starting with methyl 2-(4-amino-3-iodophenyl)acetate were synthesized with excellent yield and in-vitro screening for antimicrobial activity. The microwave synthesis offers a shorter reaction time (20-45 min), moderate reaction conditions, high returns (81%-96%), and easier operation than conventional heating. Spectroscopic techniques like 1H NMR, LCMS, IR, and 13C NMR analysis have been used to examine the structure of the newly synthesized compounds. All newly synthesized β-lactam derivatives (8a-h) were tested for antimicrobial activity against diverse bacterial and fungus strains using the broth dilution technique. Most of the investigated substances showed promising effectiveness against bacterial and fungal strains, with values ranging from 0.78 to 50 µg/mL. In contrast to the standard Ciprofloxacin for antibacterial activity and Ketoconazole for antifungal activity, compound 8c demonstrated good robust antibacterial activity against Escherichia coli and antifungal activity against Aspergillus niger with a value of 0.78 µg/mL of concentration. The final targets were performed to the inhibition of DNA gyrase by molecular docking experiments to acquire insight into relevant proteins. The results of silico molecular docks coincide with the in vitro antimicrobial investigations and may be regarded as a good DNA gyrase inhibitor.