Synthesis and biological profiling of novel quinoline-thiadiazole-thiazolone scaffolds as antimicrobial agents

The present study aimed to design and synthesize a series of quinoline-thiadiazole-thiazolone hybrid derivatives and evaluate their antibacterial and antifungal activities.

Ten derivatives (12a to 12j) were synthesized via an enaminone mediated condensation strategy and characterized using FT-IR, ¹H NMR, ¹³C NMR and mass spectrometry. Antimicrobial activity was evaluated using the agar well diffusion method against Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and fungal strains (Candida albicans, Aspergillus niger, Aspergillus clavatus). Streptomycin, ciprofloxacin, and nystatin were used as reference drugs.

All synthesized compounds exhibited measurable antimicrobial activity with varying potency. Compounds 12b and 12d showed the highest antibacterial activity, producing inhibition zones of approximately 18-22 mm against Staphylococcus aureus and 17-20 mm against Escherichia coli, which are comparable to those of standard antibiotics (20-24 mm). Moderate antifungal activity was observed against Candida albicans and Aspergillus niger, with inhibition zones of 14-17 mm, compared with nystatin (20-23 mm). Molecular docking studies supported these results by revealing favorable ligand-protein interactions for the most active derivatives.

These findings demonstrate that quinoline-thiadiazole-thiazolone hybrids represent promising scaffolds for further optimization toward the development of novel antimicrobial agents.