Insights into Novel Arylazopyrazolo[1,5-a]pyrimidines as Promising MurA Inhibitors and Antibiofilm Candidates: Design, Synthesis, Antimicrobial Evaluation, and Molecular Docking.

MurA is a pivotal target in antimicrobial therapy owing to its fundamental function in bacterial cell wall production; inhibiting this enzyme not only disrupts cell integrity, leading to bacterial lysis, but also presents a promising strategy to combat the growing threat of antibiotic resistance by providing an effective approach to both G+ve and G-ve microorganisms. Novel pyrazolo[1,5-a]pyrimidine derivatives are produced and measured for their antibacterial effectiveness. Based on the acquired findings, a majority of the examined compounds exhibited encouraging antibacterial characteristics. Among the examined compounds, 4c emerged as a standout candidate, exhibiting (MIC) = 1.95 μg/mL against Escherichia coli and demonstrating significant potency as a MurA inhibitor with (IC₅₀) of 3.77 ± 0.2 μg/mL, comparable to the established antibiotic fosfomycin. Additionally, compound 4c displayed an impressive antibiofilm activity against multiple microorganisms, indicating its potential to combat biofilm-related infections. The compound also reduced hemolysis percentage, suggesting a strong antihemolytic effect. Molecular docking studies confirm that 4c engages in crucial residues within the MurA active site, elucidating its mechanism of action.