Synthesis and Antimicrobial Evaluation of Quinoline-Pyrazolone Hybrid Derivatives as Potential Therapeutic Agents

Objective: This study aims to synthesize and evaluate the antimicrobial potential of a series of novel quinoline-pyrazolone hybrid derivatives IVa–IVj as promising therapeutic candidates against common bacterial and fungal pathogens. The growing resistance to existing antimicrobial agents highlights the urgent need for new chemical scaffolds with improved efficacy. Methods: The target compounds IVa–IVj were synthesized via a one-pot condensation reaction of substituted benzaldehydes, 4-aminoantipyrine, and 8-hydroxyquinoline. Titanium dioxide nanoparticles (TiO2 NPs), prepared by the sol-gel method, were employed as a heterogeneous catalyst under mild reaction conditions. The antimicrobial activity of the synthesized compounds was evaluated against a panel of Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and fungal strains (Candida albicans, Aspergillus niger) using the agar well diffusion method. Results and Discussion: Among the synthesized compounds, derivative IVg demonstrated the most potent antimicrobial activity, with zones of inhibition ranging from 13 to 16 mm against all tested microbial strains. Other derivatives, such as IVc, IVe, and IVi, also exhibited moderate activity. Structure–activity relationship (SAR) analysis revealed that the nature and position of substituents on the benzaldehyde ring significantly influenced biological activity, with electron-donating or bulky groups enhancing antimicrobial efficacy. Conclusions: The study successfully developed a series of quinoline-pyrazolone hybrids with promising antibacterial and antifungal properties. These compounds, particularly IVg, may serve as lead structures for the further development of novel antimicrobial agents to address the challenge of drug-resistant infections.