Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety.

To accelerate the development of novel fungicides, a variety of N-(pyrazol-5-yl)benzamide derivatives with a diphenylamine moiety were designed and synthesized using a pharmacophore recombination strategy based on the structure of pyrazol-5-yl-aminophenyl-benzamides. The bioassay results demonstrated that most of the target compounds had excellent in vitro antifungal activities against Sclerotinia sclerotiorum, Valsa mali, and Botrytis cinerea. In particular, compound 5IIIh exhibited remarkable activity against S. sclerotiorum (EC50 = 0.37 mg/L), which was similar to that of fluxapyroxad (EC50 = 0.27 mg/L). In addition, compound 5IIIc (EC50 = 1.32 mg/L) was observed to be more effective against V. mali than fluxapyroxad (EC50 = 12.8 mg/L) and comparable to trifloxystrobin (EC50 = 1.62 mg/L). Furthermore, compound 5IIIh demonstrated remarkable in vivo protective antifungal properties against S. sclerotiorum, with an inhibition rate of 96.8% at 100 mg/L, which was close to that of fluxapyroxad (99.6%). Compounds 5IIIc (66.7%) and 5IIIh (62.9%) exhibited good in vivo antifungal effects against V. mali at 100 mg/L, which were superior to that of fluxapyroxad (11.1%) but lower than that of trifloxystrobin (88.9%). The succinate dehydrogenase (SDH) enzymatic inhibition assay was conducted to confirm the mechanism of action. Molecular docking analysis further revealed that compound 5IIIh has significant hydrogen-bonding, π-π, and p-π conjugation interactions with ARG 43, SER 39, TRP 173, and TYR 58 in the binding site of SDH, and the binding mode was similar to that of the commercial fungicide fluxapyroxad. All of the results suggest that compound 5IIIh could be a potential SDH inhibitor, offering a valuable reference for future studies.

Novel N-(1H-Pyrazol-5-yl)nicotinamide Derivatives: Design, Synthesis and Antifungal Activity.

To discover more effective antifungal agents, twenty N-(1H-pyrazol-5-yl)nicotinamide derivatives were designed, synthesized, and structurally confirmed by 1 H-NMR, 13 C-NMR, and ESI-MS. All target compounds were evaluated for their antifungal activities by mycelia growth inhibition. Preliminary screening results displayed that many of these compounds had good fungicidal activity to S. sclerotiorum and V. mali. Compound B4 exhibited antifungal activity against S. sclerotiorum and V. mali with EC50 values of 10.35 and 17.01 mg/L, respectively. The experiment in vivo identified that compound B4 was effective for suppressing rape sclerotinia rot caused by S. sclerotiorum at 50 mg/L. The molecular docking study and scanning electron microscopy preliminary clarified the possible antifungal mechanism of compound B4.

Histamine-related hygienic qualities and bacteria found in popular commercial scombroid fish fillets in Taiwan.

To determine the histamine-related hygienic qualities and bacteria of scombroid fish fillets sold in traditional retail markets, 61 samples were collected from northern and southern Taiwan. It was found that the content of volatile base nitrogen in most samples was below 25 mg/100 g, which is the regulatory level in Taiwan. The ratio of unacceptable samples/total samples for aerobic plate count and Escherichia coli was 100% and 15% in northern samples and 100% and 20% in southern samples, respectively, compared with the requirements of hygienic standards. The average content of various biogenic amines in all samples were lower than 3 mg/100 g, except for histamine average content (4.6 mg/100 g) in southern samples. Among southern samples, four samples contained 12.8 to 28.8 mg/100 g histamine, which is more than 5 mg/100 g that is the allowable limit suggested by the U.S. Food and Drug Administration. Furthermore, 14 bacterial strains were isolated from sailfish fillets on a selective medium for histamine-forming bacteria. These presumptive histamine-forming strains, such as Proteus, Enterobacter, Klebsiella, Rahnella, and Acinetobacter, have been identified and found to produce 20 to 2,000 ppm histamine after incubating at 37 degrees C for 24 h.