Design, synthesis and bioactivity of a new class of antifungal amino acid‐directed phthalide compounds

Abstract

BACKGROUNDPeanut southern blight disease, caused by Sclerotium rolfsii, is a destructive soil‐borne fungal disease. The current control measures, which mainly employ succinate dehydrogenase inhibitors, are prone to resistance and toxicity to non‐target organisms. As a result, it is necessary to explore the potential of eco‐friendly fungicides for this disease.RESULTSFourteen novel phthalide compounds incorporating amino acid moieties were designed and synthesized. The in vitro activity of analog A1 (EC50=332.21 mg L‐1) was slightly lower than that of polyoxin (EC50=284.32 mg L‐1). It was observed that on the 7th day, the curative activity of A1 at a concentration of 600.00 mg L‐1 was 57.75%, while the curative activity of polyoxin at a concentration of 300.00 mg L‐1 was 42.55%. These results suggested that our compound exhibited in vivo activity. Peanut plants treated with A1 showed significant agronomic improvements compared to the untreated control. Several compounds in this series exhibited superior root absorption and conduction in comparison to the endothermic fungicide thifluzamide. The growth promotion and absorption‐conduction experiments demonstrated the reason for the superior in vivo activity of the target compound. Cytotoxic assays have demonstrated that this series of targeted compounds exhibit low toxicity levels toward human lo2 liver cells.CONCLUSIONOur results provide a new strategy for the design and synthesis of novel green compounds. Furthermore, the target compound A1 can serve as a lead for further development of green fungicides.