Synthesis and Biological Activity of Novel Antifungal Leads: 3,5-Dichlorobenzyl Ester Derivatives

Abstract

Succinate dehydrogenase (SDH) is one of the most important molecular targets for the development of new fungicides. Carboxamide fungicides are a class of SDH inhibitors widely used to inhibit highly destructive plant pathogens. Although cases of resistance have been found in fungal pathogens due to the unrestricted use in recent years, there is still demand for new compounds with improved fungicidal activity. Therefore, a series of ester compounds were designed to investigate potential novel antifungal molecules. First, the antifungal activity of different benzyl alcohol compounds (A1–A21) was tested, and a highly active fragment (3,5-dichlorobenzyl alcohol) was found. Subsequently, various compounds were synthesized by esterification between different acids and 3,5-dichlorobenzyl alcohol, among which compound 5 exhibited remarkable antifungal activity against Botrytis cinerea and Rhizoctonia solani with EC50 values of 6.60 and 1.61 mg/L, respectively, which were comparable to those of commercial fungicide boscalid (EC50 = 1.24 and 1.01 mg/L). In vivo testing further demonstrated that compound 5 was effective in suppressing B. cinerea (200 mg/L, 50.9%). Moreover, SDH inhibition assays, fluorescence quenching analysis, and determination of mitochondrial membrane potential revealed that compound 5 has similar effects to boscalid. Furthermore, the fungicidal activity of target compounds can be maintained by modifying the amide bond to an ester bond. These results will provide basis for the development of novel fungicides.

Design, Synthesis, and Antifungal Activity of Novel 1,2,4-Triazolo[4,3-c]trifluoromethylpyrimidine Derivatives Bearing the Thioether Moiety

“…The mycelial growth rates method ( Du et al, 2021 ; Wang S. et al, 2021 ) was selected to evaluate the antifungal activities of the compounds 5a–5r against six phytopathogenic fungi, including cucumber Botrytis cinerea , tobacco Botrytis cinerea , blueberry Botrytis cinerea , Phytophthora infestans , strawberry Botrytis cinerea , and Pyricularia oryzae Cav. The tested compounds were dissolved in 0.5 ml dimethyl formamide (DMF) and then added 9.5 ml sterile water to prepare the test liquids.…”

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

“…Further study revealed that compound 84 had weaker binding to the target compared to boscalid, which was consistent with findings of inhibitory activity of SDH, even though it had similar effects to boscalid. 120 This work indicated that this kind of ester compound might be novel lead compound of SDHIs and replacing amides with esters could be a successful strategy in research and development of novel SDHIs fungicides.…”

Design, Synthesis, and Bioactivities of Novel Trifluoromethyl Pyrimidine Derivatives Bearing an Amide Moiety

“…The antifungal activities against Botryosphaeria dothidea (B. dothidea), Phompsis sp., Botrytis cinereal (B. cinerea), Colletotrichum gloeosporioides (C. gloeosporioides), Pyricutaria oryzae (P. oryzae), and Sclerotinia sclerotiorum (S. sclerotiorum) of compounds 5a-5w at 50 μg/ml were determined by the typical mycelium growth rate method (Du et al, 2021;Wang W. et al, 2021), and tebuconazole was used as a positive control.…”