Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases

• Published in: Journal of agricultural and food chemistry 2019-04, Vol.67 (13), p.3535-3545
• Main Authors: Wang, Pei-Yi, Wang, Ming-Wei, Zeng, Dan, Xiang, Meng, Rao, Jia-Rui, Liu, Qing-Qing, Liu, Li-Wei, Wu, Zhi-Bing, Li, Zhong, Song, Bao-An, Yang, Song
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Imidazoles - chemistry; Imidazoles - pharmacology; Microbial Sensitivity Tests; Molecular Structure; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Plant Diseases - microbiology; Plant Diseases - prevention & control; Structure-Activity Relationship; Sulfides - chemistry; Sulfides - pharmacology; Xanthomonas - drug effects; Xanthomonas - growth & development
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.8b06242

The emergence and widespread occurrence of plant bacterial diseases that cause global production constraints have become major challenges to agriculture worldwide. To promote the discovery and development of new bactericides, imidazole-labeled 1,3,4-oxadiazole thioethers were first fabricated by integrating the crucially bioactive scaffolds of the imidazole motif and 1,3,4-oxadiazole skeleton in a single molecular architecture. Subsequently, a superior antibacterial compound A 6 was gradually discovered possessing excellent competence against plant pathogens Xanthomonas oryzae pv oryzae and Xanthomonas axonopodis pv citri with EC50 values of 0.734 and 1.79 μg/mL, respectively. These values were better than those of commercial agents bismerthiazol (92.6 μg/mL) and thiodiazole copper (77.0 μg/mL). Further modifying the imidazole moiety into the imidazolium scaffold led to the discovery of an array of potent antibacterial compounds providing the corresponding minimum EC50 values of 0.295 and 0.607 μg/mL against the two strains. Moreover, a plausible action mechanism for attacking pathogens was proposed based on the concentration dependence of scanning electron microscopy, transmission electron microscopy, and fluorescence microscopy images. Given the simple molecular structures, easy synthetic procedure, and highly efficient bioactivity, imidazole (or imidazolium)-labeled 1,3,4-oxadiazole thioethers can be further explored and developed as promising indicators for the development of commercial drugs.