Design, synthesis and antifungal evaluation of low bee-toxicity coumarin oxime derivatives

Structural modification of natural products is one of the most effective approaches for discovering new agrochemical compounds. Coumarin, a natural product, is widely found in higher plants from the Brassicaceae, Umbelliferae, Leguminosae, and Orchidaceae families. Coumarin and its derivatives exhibit a wide range of biological activities. Based on our previous research, a series of novel coumarin oxime derivatives were designed and synthesized. The preliminary mechanism of action and bee toxicity of the highly active compound were also investigated.

Most of the target compounds exhibited good antifungal activities. Compound 5k demonstrated moderate to strong broad-spectrum antifungal activities against all seven tested pathogenic fungi. Notably, it showed satisfactory antifungal activity against Rhizoctonia solani (median effective concentration = 3.29 μg/mL), surpassing the performance of the commercial coumarin fungicide osthole. In addition, the protective and curative effects of compound 5k against rice sheath blight at 200 μg/mL were 82.1% and 91.4% on detached rice leaves, and 82.5% and 72.5% on potted rice plants, respectively, outperforming osthole. Preliminary mechanistic studies suggested that compound 5k could alter mycelial morphology and increase catalase activity, promoting antioxidant and free radical scavenging functions to activate the plant's defense system. Furthermore, the median lethal dose of compound 5k was found to exceed 200 μg/bee based on an acute contact toxicity test conducted on honeybees.

This study demonstrates that coumarin oxime derivatives, with their novel structures, simple synthesis, excellent activity, and low bee toxicity, have the potential to become practical fungicides for plant protection, offering broad application prospects. © 2025 Society of Chemical Industry.