Design, synthesis, biological evaluation and DFT calculation of novel spirocyclic butenolide derivatives containing rhodanine as potential antifungal inhibitors.

BACKGROUND

The problem of resistance for fungicides has emerged in various plant pathogens and is a serious threat to crop protection. There is an urgent requirement to develop new fungicides to address the resistance issue.

RESULTS

Novel spirocyclic butenolides containing rhodanine scaffold were designed and synthesized, their structures were characterized with hyudrogen (1H) and carbon (13C) nuclear magnetic resonance (NMR) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). The in vitro antifungal activities were evaluated against five phytopathogens. These results demonstrated that most compounds exhibited remarkable antifungal activities. The median effective concentration (EC50) data of compound 4a were 0.39 μg mL‒1 (Fusarium graminearum), 0.97 μg mL‒1 (F. fujikuroi), 0.98 μg mL‒1 (Colletotrichum gloeosporioides), 0.89 μg mL‒1 (F. oxysporum vasinfectum) and 0.84 μg mL‒1 (F. oxysporum niveum), respectively. Compound 4c was the best active compound against C. gloeosporioides with an EC50 of 0.27 μg mL‒1. The in vivo antifungal activities of 4a and 4c were evaluated against C. gloeosporioides, the protective efficacies were 50.2%, 52.7% at Day 5 at a concentration of 100 μg/mL. The DFT results indicated that the two configuration isomers of target compounds have similar energies (ΔE = 0.45 kcal mol‒1), which rationalized that two configuration isomers were coexistence in a similar ratio. The results of scanning and transmission electron microscopic observation indicated that treatment with compound 4a and phenamacril had similar effects on the morphology and ultrastructure of mycelia.

CONCLUSION

The excellent in vitro and in vivo inhibitory activities of novel spirocyclic butenolides containing rhodanine against F. graminearum, F. oxysporum and C. gloeosporioides were reported, and they could be used as the potential lead compounds. © 2025 Society of Chemical Industry.