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

Abstract

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.

Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids

“…Aromatic heterocycles, particularly the imidazole ring, have been used in the last decades as structural skeletons to obtain different types of bioactive compounds with antibacterial, antifungal, anticancer, antiviral, antidiabetic, and other properties [1][2][3][4]. The search for new potent drug molecules derived from imidazole continues to be an intense area of investigation in medicinal chemistry [5][6][7]. Moreover, pharmaceutical research, manufacture, and regulation are enhancing the development of solid active ingredients, delivered as powders or tablets; however, many solid drugs which perform well in in vitro evaluation remain too insoluble for the body to absorb [8,9].…”

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

“…Their final structures were verified by NMR and high‐resolution mass spectrometry. A typical turbidimeter test was used to screen the antibacterial potency against Xoo and Xac , which are recognized as the most rambunctious and destructive pathogenic bacterial strains in agriculture. As a comparison, the commonly used antibacterial agents BT and TC were co‐assayed as the positive controls .…”

Synthesis and antibacterial and antiviral activities of myricetin derivatives containing a 1,2,4-triazole Schiff base

“…3A-C, the surface morphology of Xac was observed by scanning electron microscopy (SEM). 33,34 Bacterial cells in group (A) were rhabditiform, homogeneous in size, and unbroken in morphology. Aer treatment with 6q (12.5 mg mL À1 ), cell wall invagination appeared at both ends of the bacterial cells.…”