Design, synthesis and bioactivity studies of flavonol bio-containing β-amino alcohols

The escalating field resistance to triazole fungicides has established the development of novel, environmentally benign antifungal agents with distinct mechanisms of action, high efficacy, and low toxicity as an urgent research priority in agricultural chemistry.

Based on natural flavonol leads, a series of β-amino alcohol-containing flavonoid derivatives were synthesized and screened against nine plant pathogenic fungi. Some of them showed good inhibitory effects against Phytophthora capsici, Sclerotinia sclerotiorum, and Phytophthora kiwifruit anopheles (Phytophthora homopsis sp.). It is noteworthy that compound 5q exhibited significant inhibitory activity against P. capsici, its half-maximal effective concentration (EC₅₀) was 5.2 μg/mL, the protective and curative activities of compound 5q against eggplants were 85.7% and 77.8% at 200 μg/mL in vivo, which were better than that of azoxystrobin (Az, 42.9% and 35.5%). In addition, scanning electron microscopy (SEM) revealed that compound 5q caused mycelial breakage and crumpling, thereby disrupting normal growth. Malondialdehyde (MDA) content indicated that compound 5q compromised the integrity of fungal cell membranes, and accelerated apoptosis. Molecular docking and dynamics simulations confirmed that compound 5q binds to the cytochrome bc₁ complex with higher structural stability and compactness than Az.

Flavonols derivatives containing β-amino alcohol moieties exhibit strong potential as novel fungicidal agents. © 2025 Society of Chemical Industry.