Novel Aminocoumarin-Based Schiff Bases: High Antifungal Activity in Agriculture

Structural modification is an effective way to improve the antifungal activity of natural products and has been widely used in the development of novel fungicides. In this work, a series of aminocoumarin-based Schiff bases were synthesized and characterized by ¹H-NMR, ¹³C NMR and HR-MS spectra. The in vitro inhibition activity of all compounds was tested against four phytopathogenic fungi (Alternaria solani, Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata) using the mycelial growth rate method. The results showed that most of the target compounds exhibited significant antifungal activities. In particular, compounds 5b, 5c, 5d, 5h, 5n, 7c, 7n, and 7p exhibited more effective antifungal activity than commercially available fungicides, chlorothalonil and azoxystrobin. The structure-activity relationship revealed that the electron-withdrawing groups with more electronegativity introduced at the C-3 position were effective in improving the inhibitory activity and that halogenated benzaldehydes would be necessary in the preparation of Schiff bases. The compound 5n against Fusarium oxysporum (EC₅₀=8.73 μg/mL) and the compound 7p against Alternaria alternata (EC₅₀=26.25 μg/mL) were much better than the positive controls (chlorothalonil and azoxystrobin). Therefore, compounds 5n and 7p could serve as promising lead compounds for the development of novel broad-spectrum fungicides, which could be useful for applications in the agriculture.