Research Progress on Benzimidazole Fungicides: A Review.

Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1H-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented.

Design, synthesis, and antimicrobial evaluation of 2-aminothiazole derivatives bearing the 4-aminoquinazoline moiety against plant pathogenic bacteria and fungi.

BACKGROUND: To find more effective agricultural antibiotics, a class of new 2-aminothiazole derivatives containing the 4-aminoquinazoline moiety were synthesized and evaluated for their antimicrobial properties against phytopathogenic bacteria and fungi of agricultural importance. RESULTS: All the target compounds were fully characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry. The bioassay results showed that compound F29 with a 2-pyridinyl substituent exhibited an outstanding antibacterial effect against Xanthomonas oryzae pv. oryzicola (Xoc) in vitro, having an half-maximal effective concentration (EC50 ) value as low as 2.0 µg/mL (over 30-fold more effective than the commercialized agrobactericide bismerthiazol, with an EC50 value of 64.3 µg/mL). In addition, compound F8 with a 2-fluorophenyl group demonstrated a good inhibitory activity toward the bacterium Xanthomonas axonopodis pv. citri (Xac), around twofold more active than bismerthiazol in terms of their EC50 values (22.8 versus 71.5 µg/mL). Interestingly, this compound also demonstrated a notable fungicidal effect against Phytophthora parasitica var. nicotianae, with an EC50 value largely comparable with that of the commercialized fungicide carbendazim. Finally, mechanistic studies revealed that compound F29 exerted its antibacterial effects by increasing the permeability of bacterial membranes, reducing the release of extracellular polysaccharides, and triggering morphological changes of bacterial cells. CONCLUSION: Compound F29 has promising potential as a lead compound for developing more efficient bactericides to fight against Xoc. © 2023 Society of Chemical Industry.

Design, synthesis, crystal structure, and in vitro antibacterial activities of sulfonamide derivatives bearing the 4-aminoquinazoline moiety.

A total of 66 sulfonamide derivatives bearing the 4-aminoquinazoline moiety were designed and synthesized, and their structures were fully characterized by 1H NMR, 13C NMR, and HRMS techniques. Among them, the structures of compounds 5A10 and 5B11 were further confirmed through X-ray single-crystal diffraction analyses. The bioassay results indicated that some of the target compounds displayed higher inhibition activities in vitro against the tested phytopathogenic bacteria. For example, compound 5A26 exhibited a strong anti-Xanthomonas oryzae pv. oryzicola (Xoc) efficacy with an EC50 (half-maximal effective concentration) value of 30.6 µg/mL, over twofold more active than control agent bismerthiazol (BMT). Additionally, compound 5B14 had a good antibacterial effect against the phytopathogen Xanthomonas axonopodis pv. citric (Xac) with EC50 = 34.5 µg/mL, significantly better than control agent BMT (71.5 µg/mL). The anti-Xoc mechanistic studies showed that compound 5A26 exerted its antibacterial efficacy by increasing the permeability of bacterial membrane, decreasing the content of extracellular polysaccharides, and triggering morphological changes of bacterial cells.

Synthesis, Structural Characterization, and Antibacterial and Antifungal Activities of Novel 1,2,4-Triazole Thioether and Thiazolo[3,2-b]-1,2,4-triazole Derivatives Bearing the 6-Fluoroquinazolinyl Moiety.

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.

Carbazole sulfonamide-based macrocyclic receptors capable of selective complexation of fluoride ion.

Two carbazole sulfonamide-based macrocycles 1 and 2 were facilely synthesized and carefully evaluated for their anion recognition properties. The obtained results revealed that macrocycle 1 with a 1,3-xylyl linker was able to bind fluoride ion more strongly and selectively in acetonitrile medium than its strong competitors (like acetate and dihydrogen phosphate anions), with a large binding constant (K a) of 50 878 M-1. More importantly, an exclusive fluoride recognition was achieved for macrocycle 1 in the more polar DMSO-d 6 solution, albeit with a moderate affinity of K a = 147 M-1. Compared with macrocycle 1, macrocycle 2 bearing a 2,6-lutidinyl linkage exhibited a remarkable change not only in the anion affinity but also in the anion selectivity, although with only a slight difference in their molecular structures.

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

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.