Design, Synthesis, Crystal Structure, and Antimicrobial Evaluation of 6-Fluoroquinazolinylpiperidinyl-Containing 1,2,4-Triazole Mannich Base Derivatives against Phytopathogenic Bacteria and Fungi

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 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.

Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

“…On the other hand, 1,2,4-triazole, as an important kind of heterocyclic nitrogen compounds, is a versatile lead molecule and usually employed to design potential bioactive agents whether in the field of pesticides or medicine. This molecule and its derivatives have received considerable attention owing to a wide range of biological activities, such as anticancer ( Li et al, 2016 ; El-Sherief et al, 2018 ; Hou et al, 2019 ), antibacterial ( Gao et al, 2019 ; Shi et al, 2020 ), anti-inflammatory ( Abdel-Aziz et al, 2014 ), antiviral ( Chen et al, 2019 ), antifungal ( Xu et al, 2011 ), antitubercular ( Karczmarzyk et al, 2020 ) and other biological activities ( Mustafa et al, 2019 ; Liao et al, 2020 ; Peng et al, 2021 ). Our research group has reported the synthesis of two series of 1,2,4-triazole derivatives with potent antifungal activities ( Lin et al, 2017 ; Lin et al, 2018 ).…”

Synthesis of novel antibacterial and antifungal quinoxaline derivatives

“…1,2 For example, rice sheath blight, bacterial fruit spot of melon and bacterial blight of rice, and so forth, are difficult to control in agricultural production. [3][4][5] Rice sheath blight is one of the most widely distributed in rice and caused by RS infection. It mainly infects the leaf sheath and leaf of rice, and its symptom change from an early water damage disease spot to a moire shape.…”

Structural Modification of Saccharin Containing 2‐Aminothiazole As Potential Fungicidal Agents

“…[16] Recently, some researchers took advantage of hybridization strategy that active thiazole segment was spliced with other pharmacophore (eg. Piperidine [ , pyrazole, quinazoline, and alkaloid) [17][18][19][20][21] to design novel compounds, and further indeed discovered several potential molecules with fungicidal activities.…”