Identification of Racemic and Chiral Carbazole Derivatives Containing an Isopropanolamine Linker as Prospective Surrogates against Plant Pathogenic Bacteria: In Vitro and In Vivo Assays and Quantitative Proteomics

J Agric Food Chem. 2019 Jul 3;67(26):7512-7525. doi: 10.1021/acs.jafc.9b02036. Epub 2019 Jun 20.

Abstract

Recent observations on the emergence of drug-resistant plant pathogenic bacteria have highlighted and elicited an acute campaign to develop novel, highly efficient antibiotic surrogates for managing bacterial diseases in agriculture. Thus, a type of racemic and chiral carbazole derivative containing an isopropanolamine pattern was systematically synthesized to discover low-cost and efficient antibacterial candidates. Screening results showed that compounds 2f, 6c, and 2j could significantly suppress the growth of tested plant pathogens, namely Xanthomonas oryzae pv oryzae, X. axonopodis pv citri, and Pseudomonas syringae pv actinidiae, and provided the corresponding EC50 values of 1.27, 0.993, and 0.603 μg/mL, which were significantly better than those of existing commercial drugs. In vivo studies confirmed their prospective applications for controlling plant bacterial diseases. Label-free quantitative proteomics analysis indicated that compound 2f could dramatically induce the up- and down-regulation of a total of 247 differentially expressed proteins, which was further validated by the parallel reaction monitoring technique. Moreover, fluorescence spectra and SEM images were obtained to further explore the antibacterial mechanism.

Keywords: action mechanism; antibacterial; carbazole; isopropanolamine; proteomics.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Microbial Sensitivity Tests
  • Plant Diseases / microbiology*
  • Propanolamines / chemistry*
  • Proteomics
  • Pseudomonas syringae / chemistry
  • Pseudomonas syringae / drug effects*
  • Pseudomonas syringae / genetics
  • Pseudomonas syringae / metabolism
  • Structure-Activity Relationship
  • Xanthomonas / chemistry
  • Xanthomonas / drug effects*
  • Xanthomonas / genetics
  • Xanthomonas / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbazoles
  • Propanolamines
  • carbazole
  • monoisopropanolamine