Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Bacteria

Plant pathogens harm crops and reduce yields. We urgently need safe and effective antimicrobial agents to treat plant diseases. In this study, a series of isocryptolepine derivatives were efficiently synthesized using 4-oxoquinolinones, employing active functional group modification and bioisosteric substitution strategies. The <b>MIC</b> of compound <b>Mb-1</b> against <i>Xoo</i> was 3.12 μg/mL, which was better than that of the commercial drug copper quinolate. The <b>MICs</b> of compound <b>Mb-7</b> against <i>Xac</i> and <i>Rs</i> were 1.56 and 0.39 μg/mL respectively. In the <i>in vivo</i> antibacterial experiment, compound <b>Mb-1</b> exhibited a superior protection effect (32.7%) and therapeutic effect (31.0%) compared to copper quinolate against rice. Furthermore, compound <b>Mb-1</b> could inhibit the secretion of extracellular polysaccharides, affect biofilm formation, disrupt cell membrane integrity, increase intracellular reactive oxygen species content, and suppress the normal growth of <i>Xoo</i> and had low phytotoxicity. Thus, compound <b>Mb-1</b> is expected to be a novel broad-spectrum antibacterial candidate, which is worthy of further investigation.