Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8898
• Main Authors: Chen, Biao, Song, Dandan, Shi, Huabin, Chen, Kuai, Wu, Zhibing, Chai, Huifang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.05.2023; MDPI
• Subjects: 1,3,4-oxadiazole thioether; 4-substituted mandelic acid derivatives; Acids; Agricultural production; Antifungal activity; Antifungal Agents - chemistry; cell membrane integrity; Cell membranes; Commercialization; Crop production; Crystal structure; Economic impact; Fluorescence microscopy; Fungi; Fungicides; Fungicides, Industrial - pharmacology; Hyphae; Mandelic Acids - pharmacology; morphological study; Morphology; NMR; Nuclear magnetic resonance; Nucleic acids; Oxadiazoles; Pesticides; Phytopathogenic fungi; Plant diseases; Scanning electron microscopy; Structure-Activity Relationship; Substitutes; China; cell membrane integrity; 1,3,4-oxadiazole thioether; morphological study; 4-substituted mandelic acid derivatives; antifungal activity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108898

Plant diseases caused by phytopathogenic fungi are a serious threat in the process of crop production and cause large economic losses to global agriculture. To obtain high-antifungal-activity compounds with novel action mechanisms, a series of 4-substituted mandelic acid derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. In vitro bioassay results revealed that some compounds exhibited excellent activity against the tested fungi. Among them, the EC values of against ( ), against ( ), and against ( ) were 20.4, 12.7, and 8.0 mg/L, respectively, which were highly superior to that of the commercialized fungicide mandipropamid. The morphological studies of with a fluorescence microscope (FM) and scanning electron microscope (SEM) indicated that broke the surface of the hyphae and destroyed cell membrane integrity with increased concentration, thereby inhibiting fungal reproduction. Further cytoplasmic content leakage determination results showed a dramatic increase of the nucleic acid and protein concentrations in mycelia with treatment, which also indicated that the title compound could destroy cell membrane integrity and affect the growth of fungi. These results provide important information for further study of the mechanism of action of mandelic acid derivatives and their structural derivatization.