Sesamol derivatives bearing a quinazolin moiety: synthesis, antifungal efficacy against tea plant pathogens, and mechanistic insights

Abstract Pestalotiopsis sp. and Colletotrichum camelliae are two devastating fungal pathogens that cause significant yield losses and quality degradation in tea plants ( Camellia sinensis ). The increasing resistance of these pathogens to commercial fungicides necessitates the development of novel fungicidal agents with distinct modes of action. In this study, A series of novel sesamol derivatives incorporating a quinazolin moiety were synthesized and structurally validated by 1 H NMR, 13 C NMR, and HRMS. In vitro bioassays demonstrated that these derivatives exhibited potent antifungal activity, with compounds 4g and 4i standing out: against Pestalotiopsis sp., their inhibition rates reached 76.4% and 86.9% (vs. 18.0% for the parent compound sesamol); against C. camelliae , the rates were 57.9% and 70.8% (vs. 42.3% for sesamol). Notably, their in vivo control efficacy significantly surpassed that of azoxystrobin: 4g and 4i controlled C. camelliae with efficiencies of 66.6% and 51.7% (vs. 25.7% for azoxystrobin) and Pestalotiopsis sp. with 99.0% efficacy (vs. 57.1% for azoxystrobin). Mechanistic investigations revealed dual modes of action: (i) direct disruption of fungal cell membrane integrity; (ii) induction of tea plant resistance via up-regulating activities of defense-related enzymes (PAL, POD, SOD, CAT). Integrated transcriptomic and proteomic analyses further confirmed that 4g activates classical defense pathways by coordinately regulating defense gene expression and protein synthesis. In summary, these sesamol-quinazolin hybrids demonstrate potent antifungal activities with multiple targets. This study not only expands the application scope of the natural product sesamol but also provides promising lead compounds for the development of eco-friendly fungicides in tea plant protection.