Microwave-Irradiated Eco-Friendly Multicomponent Synthesis of Substituted Pyrazole Derivatives and Evaluation of Their Antibacterial Potential

The synthesis of novel pyrazole derivatives (SPDs) and their evaluation for antibacterial potential against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae) was developed herein. These compounds were obtained via a microwave-assisted eco-friendly multicomponent reaction (MCR) and were characterized for structural confirmation using 1H NMR, 13C NMR, 2D experiments, TOF-MS, and FTIR spectrometry. Antibacterial activity, as measured by minimum inhibitory concentrations (MICs) of SPDs, ranged between 0.212 and 2.50 mg/mL against S. aureus, S. pneumoniae, P. aeruginosa, and E. coli. Compound 4e was the most potent against S. pneumoniae, with an MIC value of 0.0156 mg/mL compared with Amoxicillin’s MIC value of 0.0306 mg/mL. Thus, compound 4e was observed as a potential lead candidate against S. pneumoniae. Further corroboration by molecular docking at the active site of the key penicillin-binding protein (PBP) revealed that the most potent compounds against each organism showed comparable docking scores to those of amoxicillin. In addition, a pharmacokinetics study showed that synthesized SPDs were predicted to be orally bioavailable and non-inhibitors of cytochrome 3A4 and belong to drug classes 4 and 6. Hence, they were suitable for drug development and warrant further studies such as in vitro assays, in silico modeling, DFT studies, and machine learning for drug design.