Synthesis, Bioactive Evaluation, and Preliminary Antibacterial Mechanism Study of Novel Ferulic Acid Derivatives

Objective: The aim of this study was to design and synthesize a series of ferulic acid derivatives containing amide moieties and to evaluate their activity against plant pathogenic bacteria. Methods: The structures of the synthesized compounds (IIIa–IIIy) were thoroughly characterized using ¹H, ¹³C NMR, and HR-MS techniques. The antibacterial activity of the target compounds against Xanthomonas oryzae pv. oryzicola (Xoc), Pseudomonas syringae pv. actinidiae (Psa), and Xanthomonas axonopodis pv. citri (Xac) was evaluated in vitro using the turbidity method. Results and Discussion: The bioassay results indicated that some of the target compounds exhibited enhanced inhibitory activity against the tested phytopathogenic bacteria. In particular, compound (IIId) demonstrated potent activity against Xoc, with an EC₅₀ value of 24.4 μg/mL, which is more than three times more active than the reference agent thiodiazole copper (EC₅₀ = 86.7 μg/mL). Additionally, compound (IIId) showed significant antibacterial activity against Psa, with an EC₅₀ of 55.4 μg/mL, outperforming the reference compound zinc thiazole (EC₅₀ = 102.2 μg/mL). Mechanistic studies suggested that compound (IIId) exerts its antibacterial effect by increasing bacterial membrane permeability, reducing exopolysaccharide content, and inducing morphological alterations in bacterial cells. In vitro cytotoxicity assays indicated that compound (IIId) is essentially non-toxic to mammalian cells. Conclusions: Compound (IIId) exhibits promising potential as a lead compound for the development of more effective agricultural antibacterial agents to control Xoc in the future.