Synthesis and evaluation of imidazo[1,2-a]quinoxaline derivatives as potential antifungal agents against phytopathogenic fungi.

ABSTRACT

To discover novel and effective potential agricultural antifungal agents, various kinds of imidazo[1,2-a]quinoxaline derivatives were designed, and synthesized from available and inexpensive reagents. Their antifungal activities were first evaluated against ten typical phytopathogenic fungi. The in vitro antifungal activity showed that some compounds exhibited more obvious broad-spectrum fungicidal activity than the two commercially-available fungicides chlorothalonil and hymexazol. Valsa mali and Botrytis cinerea strains exhibited the highest susceptibility with EC50 values of 1.4-27.0 µg/mL to more than ten compounds. Compounds 5c and 5f showed the most promising inhibitory effects against Valsa mali (EC50 = 5.6 µg/mL) and Fusarium solani (EC50 = 5.1 µg/mL), respectively. Preliminary studies on the mechanism of action indicated that the imidazo[1,2-a]quinoxaline skeleton likely exerted its antifungal effects by disrupting hyphal differentiation, spore germination, and germ tube growth. Moreover, the cell experiment results indicated that these target compounds possessed good safety to BV2 cells. Overall, compounds 5c and 5f can be considered candidate compounds against specific fungi for further detailed research. This study can provide a theoretical basis for the application of imidazo[1,2-a]quinoxaline scaffolds as novel fungicides in agriculture.