Novel Flavonol Derivatives Bearing a 1,2,3,4-Tetrahydroquinoline Moiety: Design, Synthesis, and Anti- Phytophthora capsici Activity

Abstract

Twenty-three novel flavonol derivatives bearing a 1,2,3,4-tetrahydroquinoline (THQ) scaffold were designed and synthesized, and their antifungal activities against eight plant pathogenic fungi were evaluated. Several compounds exhibited 100% inhibition against Sclerotinia sclerotiorum and Phytophthora capsici (Pc). Among them, Q8 showed the most potent activity against Pc with an EC50 value of 4.1 μg mL–1, superior to azoxystrobin (69.0 μg mL–1) and fluopyram (123.2 μg mL–1). In vivo tests on chili fruits demonstrated that Q8 at 200 μg mL–1 provided superior curative and protective effects (73.7 and 80.8%) compared to azoxystrobin (53.0 and 54.4%). Mechanistic studies revealed that Q8 disrupted cell membrane integrity and inhibited succinate dehydrogenase (SDH) activity, with computational simulations suggesting a higher binding affinity for SDH than fluopyram. Safety evaluation showed no obvious adverse effects on seed germination or earthworm survival. Collectively, these results indicate that Q8 represents a promising lead compound for fungicide development.