Design, synthesis, molecular properties and antimicrobial activities of some novel 2(3H) pyrrolone derivatives

Abstract

In continuation of our research on nitrogen containing heterocyclic compounds to develop potent antimicrobial and antimycobacterial agents, some novel 2(3H) pyrrolone derivatives were synthesized. We report here two new series of 3-Arylidene-5-(4-chloro/methyl phenyl)-2(3H) pyrrolones (14–19) and 3-Arylidene-5-(4-chloro/methyl phenyl)-1-benzyl-2(3H) pyrrolones (20–25) prepared by reacting intermediate furanone compounds (6–13) with ammonia gas and benzylamine respectively. The structures of the title compounds were established on the basis of IR, 1H NMR, mass spectral data and elemental analysis results. All the synthesized pyrrolone derivatives were evaluated for their possible antibacterial, antifungal and antitubercular activities. Among all the synthesized compounds, compound 17, 3-(4-Hydroxy-3-methoxybenzylidene)-5-(4-chlorophenyl)-2(3H)-pyrrolone, emerged as a lead compound exhibiting the highest antibacterial, antifungal and antitubercular activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Mycobacterium tuberculosis with 6.25 μg/mL MIC (minimum inhibitory concentration). Molecular properties of pyrrolones were also calculated by Molinspiration software for drug likeness. It was observed that all 2(3H) pyrrolones (14–19) obeyed Lippinski’s rule of five and expected to be orally active. They were also found to be more potent antimicrobial agents than 1-benzyl-2(3H) pyrrolones (20–25) and their activity was comparable with standard drugs such as Ciprofloxacin, Ketoconazole and Streptomycin.