Synthesis of novel 18β-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases

BACKGROUND The limited amount of agrochemicals targeting plant bacterial diseases has motivated us to study innovative antibacterial surrogates with fresh modes of action. Notably, fabrication of violent apoptosis inducers to control the reproduction of pathogenic bacteria should be a feasible way to control plant bacterial diseases. To achieve this aim, we constructed a series of novel 18 beta-glycyrrhetinic piperazine amides based on the natural bioactive ingredient 18 beta-glycyrrhetinic acid to evaluate the in vitro and in vivo antibacterial activity and induced apoptosis behaviors on tested pathogens. RESULTS Screening results suggested that these designed compounds were extremely bioactive against two notorious pathogens, Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. This conclusion was highlighted by the biological effects of compounds A(3) and B-1, affording the related EC50 values of 2.28 and 0.93 mu g mL(-1). In vivo trials confirmed the prospective application for managing rice bacterial blight disease with control efficiency within 50.57-53.70% at 200 mu g mL(-1). In particular, target compounds could induce the generation of excessive reactive oxygen species (ROS) in tested pathogens, subsequently leading to a strong apoptotic effect at a very low drug concentration (<= 10 mu g mL(-1)). This finding was consistent with the observed ROS-enhanced fluorescent images and morphological changes of pathogens from scanning electron microscopy patterns. CONCLUSION Given these features, we anticipate that these novel piperazine-tailored 18 beta-glycyrrhetinic hybrids can provide an perceptible insight for fighting bacterial infections by activation of the apoptosis mechanism. Novel 18 beta-glycyrrhetinic piperazine amides were reported to have excellent antibacterial efficacy toward phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. A possible apoptosis mechanism was proposed from the remarkable apoptotic behaviors triggered by target compounds.