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 <b>5h</b> could significantly suppress the growth of tested plant pathogens, namely, <i>Xanthomonas</i> <i>oryzae pv oryzicola</i> (<i>Xoc</i>) and <i>Xanthomonas oryzae pv oryzae</i> (<i>Xoo</i>), and provided the corresponding EC₅₀ values of 1.53 and 6.07 μg/mL, indicating a higher efficacy compared to allicin and kasugamycin. Moreover, <b>5h</b> exhibited 80.9% curative effects and 51.3% protective effects against <i>Xoc</i> 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 <b>5h</b> can therefore be considered as a potential candidate antibacterial agent to manage plant bacterial diseases.