Design, Synthesis, Crystal Structure, and Antimicrobial Evaluation of 6-Fluoroquinazolinylpiperidinyl-Containing 1,2,4-Triazole Mannich Base Derivatives against Phytopathogenic Bacteria and Fungi
Jun Shi, Muhan Ding, Na Luo, Suran Wan, Peijia Li, Junhong Li, Xiaoping Bao
Abstract
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 EC50 values of 23.6, 18.8, 23.4, and 24.3 μg/mL, respectively, which were far superior to that of agrobactericide bismerthiazol (EC50 = 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 1,2,4-triazole Mannich base derivatives as effective bactericides for controlling Xoo.