New Benzofuran–Pyrazole-Based Compounds as Promising Antimicrobial Agents: Design, Synthesis, DNA Gyrase B Inhibition, and In Silico Studies

Background/Objectives: The alarming rise in antibiotic resistance necessitates the discovery of novel antimicrobial agents. This study aims to design, synthesize, and evaluate new benzofuran–pyrazole-based compounds for their antimicrobial, antioxidant, and anti-inflammatory properties. Methods: New benzofuran–pyrazole hybrid molecules were synthesized using the Vilsmeier–Haach reaction and other chemical processes. The structures of the synthesized compounds were confirmed through micro-analytical and spectral analyses. Their antimicrobial activities were assessed against various bacterial and fungal strains, while antioxidant and anti-inflammatory properties were evaluated using DPPH-free radical scavenging and HRBC membrane stabilization assays, respectively. The most promising compounds were further tested for DNA gyrase B inhibition. Results: Compounds 9, 10, and 11b–d exhibited significant broad-spectrum antimicrobial activity with MIC values ranging from 2.50 to 20 µg/mL. Compounds 4, 6, 9, 11b, and 11d demonstrated high antioxidant activity, with DPPH scavenging percentages between 84.16% and 90.52%. Most compounds showed substantial anti-inflammatory effects, with HRBC membrane stabilization percentages ranging from 86.70% to 99.25%. Compound 9 notably inhibited E. coli DNA gyrase B with an IC50 of 9.80 µM, comparable to ciprofloxacin. Conclusions: The benzofuran–pyrazole-based compounds, particularly compound 9, show great potential as new antimicrobial agents due to their broad-spectrum activity and potent DNA gyrase B inhibition. These findings support further development and optimization of these compounds for clinical applications.