Synthesis and Evaluation of Novel Harmine Derivatives with 6-Piperazine Moieties as Potential Antimicrobial Agents

A series of 6-piperazine harmine derivatives were designed and synthesized, and their antibacterial activities against plant phytopathogenic bacteria were evaluated for the development of β-carboline bactericides. Screening results showed that compound 5h could significantly suppress the growth of tested plant pathogens, namely, Xanthomonas oryzae pv oryzicola (Xoc) and Xanthomonas oryzae pv oryzae (Xoo), and provided the corresponding EC₅₀ values of 1.53 and 6.07 μg/mL, indicating a higher efficacy compared to allicin and kasugamycin. Moreover, 5h exhibited 80.9% curative effects and 51.3% protective effects against Xoc at the dose of 100 μg/mL in vivo, significantly surpassing those of allicin (33.2%, 28.3%) and kasugamycin (11.7%, 6.0%). Further studies of antibacterial mechanism were also carried out, including scanning electron microscope observations, permeability of bacterial membrane, extracellular polysaccharide production, biofilm formation, motility, transcriptome analysis, and RT-qPCR validation. Overall, given these excellent profiles, 6-piperazine harmine derivative 5h can therefore be considered as a potential candidate antibacterial agent to manage plant bacterial diseases.