Synthesis and agricultural antimicrobial evaluation of new quinazoline derivatives containing both a piperazine linker and the N‐acetyl moiety

• Published in: Pest management science 2024-10, Vol.80 (10), p.5307-5321
• Main Authors: An, Lian, Yang, Lan, Yan, Taisen, Yi, Mingyan, Liu, Songsong, Li, Hong, Bao, Xiaoping
• Format: Article
• Language: English
• Subjects: antibacterial activities; Antiinfectives and antibacterials; Antimicrobial agents; Bacteria; Bactericides; Bioassays; Biosynthesis; Cell morphology; Cellulase; Cytoplasmic membranes; Enzymatic activity; Flagella; Fungicides; Industrial development; Mass spectrometry; Mass spectroscopy; mechanisms of action; Membrane permeability; Motility; NMR; Nuclear magnetic resonance; N‐acetyl moiety; Piperazine; piperazine linker; Polysaccharides; Proteomics; quinazoline derivatives; Saccharides; Single crystals; Swimming; X-ray diffraction
• ISSN: 1526-498X; 1526-4998; 1526-4998
• DOI: 10.1002/ps.8256

BACKGROUND To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N‐acetyl moiety were prepared and assessed for their antibacterial and antifungal activities. RESULTS All the target compounds were characterized by 1H and 13C NMR as well as high‐resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4‐trifluoromethoxy substituent was clearly confirmed via single crystal X‐ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15‐ and 10‐fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC50 = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down‐regulating the expression of the related differential proteins. CONCLUSION Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry. A class of new quinazoline derivatives containing both a piperazine linker and the N‐acetyl moiety were synthesized and assessed for their agricultural antibacterial and antifungal activities. Among them, compound E19 was identified as an excellent bactericide in vitro and in vivo for control of Xanthomonas oryzae pv. oryzicola.