Design, Synthesis and Antimicrobial Evaluation of Novel Tyrosine Derivative N-Acylhydrazones

Background and Aims: The alarming rates of antimicrobial resistance necessitate the urgent discovery of new antimicrobial agents with broad-spectrum activity against both bacteria and fungi. Therefore, the aim of this study was to evaluate the in vitro antimicrobial activities of L-tyrosine-derived N-acylhydrazones against various Gram (+)/Gram (-) bacterial strains as well as Candida albicans.Methods: Starting from L-tyrosine, esterification followed by amidation with a 2,4-dichlorobenzoyl moiety was performed. Subsequently, the corresponding hydrazides were synthesised. Finally, the hydrazides were converted into N-acylhydrazone derivatives (5a–h). The structures and purities of all compounds were confirmed by spectral analyses, including FTIR, ¹H NMR, ¹³C NMR-APT, LC-MS, and/or HRMS. The in vitro antimicrobial activities of compounds 5a–h were evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and C. albicans. In addition, the in silico physicochemical properties of compounds 5a–h were predicted using the QikProp module (Schrödinger).Results: Compound 5c, bearing a 3-fluorobenzylidene moiety, exhibited the highest antimicrobial activity against S. aureus with a MIC value of 19.53 μg/mL. In addition, compound 5c displayed activity against S. epidermidis and E. coli. Furthermore, compound 5f, containing a 3,4-dimethoxybenzylidene moiety, demonstrated moderate antibacterial efficacy against S. aureus, S. epidermidis, and E. coli. Based on the in silico physicochemical evaluations, all compounds (5a–h) were generally consistent with RO5, except for deviations in logPo/w and molecular weight parameters observed in some derivatives.Conclusion: L-tyrosine-derived N-acylhydrazones exhibit improvable antimicrobial potential, and this scaffold remains open for further optimisation in both antimicrobial efficacy and physicochemical properties.