Discovery and Mechanism of Azatryptanthrin Derivatives as Novel Anti-Phytopathogenic Bacterial Agents for Potent Bactericide Candidates.

The natural alkaloids of tryptanthrin and their derivatives have a wide range of biological activities. In this research, four series of azatryptanthrin derivatives containing 4-aza/3-aza/2-aza/1-aza tryptanthrin were prepared by condensation cyclization reaction against plant pathogens to develop a new natural product-based bacterial pesticide. Compound displayed a remarkable growth inhibitory effect on pathogenic bacteria of pv. (), pv. (), and pv. () with the final corrected EC values of 0.312, 1.91, and 18.0 μg/mL, respectively, which were greatly superior than that of tryptanthrin (Tryp). Moreover, also showed effective therapeutic and protective activities in vivo on citrus canker. Further mechanism studies on elucidated that compound was able to affect the growth curve of and the formation of biofilm, cause severe shrinkage in bacterial morphology, increase reactive oxygen species levels, and induce apoptosis in bacterial cells. Quantitative analysis of differential protein profiles found that the major differences were mainly concentrated on the endometrial protein in the bacterial secretion system pathway, which blocked the membrane transport and affected the transfer of DNA to the host cell. In summary, these research results suggest that represents a promising anti-phytopathogenic-bacteria agent, which is worth being further investigated as a bactericide candidate.