Discovery of bioactive aromatic butenamide derivatives: synthesis, antifungal activity, and mechanistic elucidation

Abstract

Plant pathogenic fungi pose a serious threat to global agricultural production. Traditional fungicides have become increasingly prominent due to multi-drug resistance. It is urgent to develop new and efficient fungicides with unique mechanisms of action that can effectively overcome drug resistance. The structures of the synthesized compounds were characterized by 1 H NMR, 13 CNMR, and ESI–MS. Their antifungal activity was evaluated using the microbroth dilution method, and the target compounds with better antifungal effect were screened out. The mechanism of action was investigated by Scanning Electron Microscopy (SEM) combined with physiological and biochemical analyses. At the same time, further research is carried out through molecular docking simulation. Four aromatic butenamide derivatives were synthesized, and all structural characterizations were completed, with yields ranging from 19.5 to 56.6%. The antifungal activity results showed that compound 1 exhibited the strongest activity (MIC  =  5 mg/mL), followed by compound 2 (MIC  =  6.5 mg/mL), while compounds 3 and 4 showed weaker effects (MIC  =  30 mg/mL and 31.25 mg/mL, respectively). The mechanism of compound 1 with activity was studied. It was found that compound 1 could destroy the integrity of fungal cell membrane and cause the leakage of intracellular substances. At the same time, it disrupts the dynamic balance of antioxidant enzymes and inhibits the normal physiological metabolism of fungi. The molecular docking results confirmed that the binding of the four derivatives to Succinate Dehydrogenase was generally more stable than that of Chitin Synthase. This study can provide clear guidance for the design and optimization of aromatic butenamide derivatives.