A total of 20 1,2,4-triazole Mannich base derivatives bearing the 6-fluoroquinazolinylpiperidinyl moiety were designed, synthesized, and evaluated as antimicrobial agents against phytopathogenic bacteria and fungi according to the molecular hybridization strategy. Of note, the structure of target compound 4h was clearly confirmed through single-crystal X-ray diffraction analysis. The turbidimetric assays indicated that some compounds exhibited excellent antibacterial efficacies in vitro against Xanthomonas oryzae pv. oryzae (Xoo). For example, compounds 4c, 4f, 4j, and 7j had EC 50 values of 23.6, 18.8, 23.4, and 24.3 μg/ mL, respectively, which were far superior to that of agrobactericide bismerthiazol (EC 50 = 92.4 μg/mL). In particular, compound 4f demonstrated a potent anti-Xoo activity approximately five times more active than that of bismerthiazol. Moreover, in vivo assays showed the excellent protective and curative activities of compound 4f against rice bacterial blight, having the potential as an alternative bactericide for controlling Xoo. The structure−activity relationship analysis showed a good pesticide-likeness concerning compound 4f, following Tice's criteria. The anti-Xoo mechanism of compound 4f was preliminarily explored by scanning electron microscopy measurements in living bacteria. Finally, several compounds also exhibited good antifungal activities in vitro against Gibberella zeae at 50 μg/mL. In short, the presented work showed the potential of 6-fluoroquinazolinylpiperidinyl-containing 1,2,4triazole Mannich base derivatives as effective bactericides for controlling Xoo.

A total of 52 novel 1,2,4-triazole thioether and thiazolo­[3,2-b]-1,2,4-triazole derivatives bearing the 6-fluoroquinazolinyl moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture based on the molecular hybridization strategy. Among them, molecular structures of compounds 5g and 6m were further confirmed via the single-crystal X-ray diffraction method. The bioassay results indicated that some of the target compounds possessed excellent antibacterial activities in vitro against the pathogen Xanthomonas oryzae pv. oryzae (Xoo). For example, compound 6u demonstrated a strong anti-Xoo efficacy with an EC50 value of 18.8 μg/mL, nearly 5-fold more active than that of the commercialized bismerthiazol (EC50 = 93.6 μg/mL). Moreover, the anti-Xoo mechanistic studies revealed that compound 6u exerted its antibacterial effects by increasing the permeability of bacterial membrane, reducing the content of extracellular polysaccharide, and inducing morphological changes of bacterial cells. Importantly, in vivo assays revealed its pronounced protection and curative effects against rice bacterial blight, proving its potential as a promising bactericide candidate for controlling Xoo. Moreover, compound 6u had a good pesticide-likeness based on Tice’s criteria. More interestingly, compound 6u with high anti-Xoo activity also demonstrated a potent inhibitory effect of 80.8% against the fungus Rhizoctonia solani at 50 μg/mL, comparable to that of the commercialized chlorothalonil (85.9%). Overall, the current study will provide useful guidance for the rational design of more efficient agricultural antimicrobial agents using the thiazolo­[3,2-b]-1,2,4-triazole derivatives bearing the 6-fluoroquinazolinyl moiety as lead compounds.

Two carbazole sulfonamide-based macrocycles 1 and 2 were facilely synthesized and carefully evaluated for their anion recognition properties.

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