To discover more effective antifungal candidates, 33 benzoxazole derivatives, were designed, synthesized, and evaluated for their antifungal activity against seven phytopathogenic fungi by the mycelium growth rate method. Among 33 benzoxazole derivatives had thirteen derivatives no reported, and new derivatives C17 exhibited good inhibitory activity against Phomopsis sp. with EC50 values of 3.26 μM. Structure-activity relationship (SAR) of these derivatives analysis indicated that the substituent played a key role in antifungal activity in ortho-, meta- and para- substituted acetophenones. The preliminary mechanistic exploration demonstrated that C17 might exert its antifungal activity by targeting the mycelia cell membrane, which was verified by the observed changes in mycelial morphology, the formation of extracellular polysaccharides, cellular contents, cell membrane permeability and integrity, among other effects. Furthermore, C17 had potent curative effect against Phomopsis sp. in vivo, which indicated that C17 may be as a novelty potent antifungal agent.
Keywords: antifungal activity; benzoxazole; benzoxazole derivatives design and synthesis; primary mechanism; structure-activity relationships.
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