Synthesis and Antifungal Activity of New butenolide Containing Methoxyacrylate Scaffold

Abstract

In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by 1H NMR, 13C NMR, HR-MS spectra, and X-ray diffraction analysis. The in vitro antifungal activities were evaluated by the mycelium growth rate method. The results showed that the inhibitory activities of these new compounds against Sclerotinia sclerotiorum were significantly improved, in comparison with that of the lead compound 3–8; the EC50 values of V-6 and VI-7 against S. sclerotiorum were 1.51 and 1.81 mg/L, nearly seven times that of 3–8 (EC50 10.62 mg/L). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound VI-3 had a significant impact on the structure and function of the hyphal cell of S. sclerotiorum mycelium and the positive control trifloxystrobin. Molecular simulation docking results indicated that the introduction of methoxyacrylate scaffold is beneficial to improving the antifungal activity of these compounds against S. sclerotiorum, which can be used as the lead for further structure optimization.

Design, Synthesis, and Antifungal/Antioomycete Activity of Thiohydantoin Analogues Containing Spirocyclic Butenolide

“…The key intermediates 3 were prepared following the protocol in our previous works by the reaction of 2 and diketene. − Compounds 3a , 3b , 3d , 3e , 3h , and 3p have been synthesized as our previous report. , …”

“…In order to observe the influence of compound 5j on the mycelial morphology of P. capsici, SEM was performed following the method in our previous work. , In brief, active P. capsici mycelial tips (5 mm) treated with compound 5j (0.38 μg/mL) were cut from the edge of the colony incubated at 25 °C for 48 h. The tips were treated with 4% glutaraldehyde at 4 °C, washed with 0.1 M phosphate buffer (pH 7.3), and fixed with 1% w/v osmium tetraoxide solution.…”

“…Molecular docking was conducted by the SYBYL-X 2.0 software following the protocol described previously. ,, The structure of bovine mitochondrial cytochrome bc 1 complex (PDB: 1L0L) was obtained from the RCSB Protein Data Bank. The ligand famoxadone in the ubiquinol oxidation site of cytochrome bc 1 complex was extracted, and all water molecules were also removed.…”