Design, Synthesis, and Biological Activity Studies of Flavonol Derivatives Containing Pyrazolamide Structure

Abstract

A series of flavonol derivatives with pyrazole amide were synthesized, and their antifungal activity was tested against 9 fungi in this study. Most compounds showed strong inhibitory effect against Phytophthora capsici. Notably, J13 exhibited the highest inhibition against Pc (EC₅₀ = 6.29 μg/mL), significantly outperforming azoxystrobin (96.5 μg/mL) and fluopyram (FI, 127.95 μg/mL). In vivo antioomycete experiments with J13 were conducted on chili fruits, leaves, and eggplant. In vivo tests on chili leaves revealed that J13 (200 μg/mL) provided superior curative (89.4%) and protective (87.2%) effects compared to FI (47.9 and 33.7%). J13 caused damage to the cell membranes of Pc hyphae, as observed in scanning electron microscopy (SEM) and fluorescence microscopy (FM) experiments. This membrane disruption was further confirmed by detecting cytoplasmic leakage, assessing membrane permeability, and measuring the malondialdehyde (MDA) content. Furthermore, J13 induced mitochondrial dysfunction, manifested as altered mitochondrial membrane potential and reduced succinate dehydrogenase (SDH) activity; molecular docking and molecular dynamics simulations demonstrated stable binding of J13 to the SDH protein. Moreover, J13 demonstrated favorable biosafety toward both target plants and nontarget organisms. These experimental results lay the groundwork for innovative strategies to develop novel environmentally friendly fungicides.