Design, Synthesis And Biological Activity Of Novel Carbazole Compounds Containing Isopropanolamine Structur

The increasing resistance problems of pathogens have drastically reduced the efficiency of existing drugs and agricultural chemicals,increasing the difficulty of preventing and controlling bacterial diseases.To discovery effective bactericide alternatives,a series of novel 3-（piperazin-1-yl）propan-2-ol decorated carbazole derivatives was fabricated,and their bioactivities and drug-likeness properties were evaluated.In vitro bioassays showed that target molecules of route A had outstanding antibacterial activity against Xanthomonas oryzae pv.oryzae（Xoo）,Xanthomonas axonopodis pv.citri（Xac）,and Pseudomonas syringae pv.actinidiae（Psa）,with optimal EC₅₀ values of 6.80μg/mL（A₉）,6.37μg/mL（A₉）,and 10.75μg/mL(A₁₀),respectively.In vitro bioassays showed that target molecules of route B had outstanding antibacterial activity against Xoo,Xac,and Psa,with optimal EC₅₀ values of 3.11μg/mL(B₁₆),3.20μg/mL(B₁₆),and 3.54μg/mL(B₁₆),respectively.The in vivo activity of compound B₁₆ against rice bacterial blight and kiwifruit canker pathogen was tested separately.Bioassay results showed that compound B₁₆had activity against rice rice bacterial blight at 200μg/mL.It could protect 35.12%of samples and cure 38.56%of samples,and was more efficacious than the commercial bactericide TC（27.06%and 17.50%,respectively）.Compound B₁₆ possessed excellent protective activity against kiwifruit bacterial canker at 200μg/mL.It could protect 67.61%of samples[superior to that of TC（45.07%）]and could cure 45.54%of samples[superior to that of TC（47.89%）].Furthermore,a series of biochemical assays indicated that title molecules could negatively impact the function of bacteria by irreversibly damaging their cell membranes,resulting in cytoplasmic components leakage（nucleic acids and proteins）.In addition,phytotoxicity test and in silico toxicity predictions suggested that compound A₉ had low phytotoxicity,and possessed acceptable drug-like properties.Our results showed that carbazole derivatives containing an3-（piperazin-1-yl）propan-2-ol moiety were promising skeletons to develop novel bactericides with low toxicity for controlling refractory microbial diseases by targeting cell membranes.