Synthesis, Spectral Characterisation and Docking Analysis of Thiazole-Based Schiff Base Derivatives as Novel Antimicrobial and Antifungal Agents

Abstract

A novel series of thiazole-based Schiff base derivatives (ML-1 to ML-10) were synthesised via condensation of 2-aminothiazole with N-Boc-protected amino acids, followed by deprotection and reaction with various aromatic aldehydes. Structures were confirmed by FT-IR, ¹H NMR, ¹³C NMR and mass spectrometry. The antibacterial activity of all the compounds was evaluated against six bacterial strains, showing that ML-9 exhibited the strongest activity, with ML-9 exhibiting the strongest activity, showing MIC values within the range of ciprofloxacin against selected strains. The antifungal activity was also assessed against Fusarium oxysporum, Rhizoctonia solani and Colletotrichum capsici, with ML-9 showing the most potent inhibition with ML-9 showing the lowest MIC values, approaching those of fluconazole against Rhizoctonia solani and Colletotrichum capsici. SAR studies highlighted the importance of electron-donating and -withdrawing groups in enhancing activity. Molecular docking against CYP51 (PDB ID: 4WMZ) revealed strong binding for ML-9 and ML-8 (G-scores: -6.735 and -6.560 kcal/mol), with stable interactions involving LEU380, PHE384 and TYR140. These results identify ML-9 and ML-8 as promising preliminary candidates for further structural optimisation and biological evaluation.