Structural Simplification of Cryptolepine to Obtain Novel Antifungal Quinoline Derivatives against Phytopathogenic Fungi.

A series of quinoline derivatives were designed and synthesized by the structural simplification of cryptolepine and evaluated for their fungicidal activity against six phytopathogenic fungi. Most of these compounds exhibited remarkable activities against Botrytis cinerea in vitro . Among them, compounds A18 and L01 showed superior antifungal activity. Significantly, compared to cryptolepine, compound A18 exhibited broad-spectrum inhibitory activities against B. cinerea , Sclerotinia sclerotiorum , Rhizoctonia solani , Phytophthora capsica , Magnaporthe oryzae , and Fusarium graminearum with the respective EC 50 values of 0.249, 1.569, 3.915, 0.505, 0.246, and 4.999 μg/mL. Compound L01 displayed the best antifungal activity against B. cinerea with an EC 50 value of 0.156 μg/mL. Preliminary mechanistic studies showed that compound A18 could inhibit spore germination, affect the permeability of the cell membrane, increase the content of reactive oxygen species, and affect the morphology of hyphae and cells. Moreover, compound A18 showed excellent in vivo protective effect against B. cinerea , which was more potent than pyrimethanil and equitant to cryptolepine. These results evidenced that compound A18 displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.