Synthesis, antimicrobial evaluation, and in silico studies of some novel hydrazinylquinoline and pyrazoline derivatives as potential antimicrobial agents

Abstract Antimicrobial resistance remains a major global public health challenge, contributing to increased mortality rate and treatment failures in an effort to address this growing challenge, the present research work focused on the synthesis and evaluation of new hydrazone scaffold and pyrazoline derivatives (coded HS6–HS10) as potential antimicrobial agents. The target compounds were synthesized via one-pot condensation reactions and characterized using FTIR, 1 H, and 13 C NMR techniques. Their antimicrobial activities were assessed in vitro against a panel of Gram-positive, Gram-negative bacteria, and fungal strains. However, their assessment revealed broad spectrum of antimicrobial activity, where the compounds bearing biaryl-substituted hydrazones with electron-donating or electron-withdrawing groups at para- and or meta-positions showed highest potency. However, MIC values of 12.5 mg/mL were observed against clinical isolates such as E. coli , S. typhi , and P. aeruginosa , while S. aureus , B. subtilis , and S. pneumoniae were inhibited at 12.5–25 mg/mL, while MIC values of 50 mg/mL were recorded against Aspergillus niger , indicating weak antifungal activity. The molecular docking studies conducted using target microbial enzymes such as dihydrofolate reductase (DHFR) and squalene epoxidase (SQLE) against the ligands HS7 and HS8 have strong binding affinities towards DHFR (− 9.6 and − 9.4 kcal/mol) and SQLE (− 9.8 and − 10.2 kcal/mol), respectively, outperforming standard reference drugs ciprofloxacin (− 7.4 kcal/mol) and terbinafine (− 9.8 kcal/mol). Meanwhile, the in silico ADME analysis confirmed that all compounds satisfied Lipinski’s rule of five, suggesting favourable drug-like properties. In conclusion, these findings suggest that substituted hydrazone and pyrazoline derivatives possess considerable promising scaffolds for developing better novel antimicrobial agents that are capable of combating resistant pathogens.