Synthesis, Bioactivity, and Mechanistic Insights of Novel Arecoline-Fused Quinazoline Derivatives as Potential Agents for Controlling Tea Tree Fungal Diseases

<i>Pestalotiopsis</i> species and <i>Colletotrichum camelliae</i> threaten tea production. With limited effective controls and rising pathogen resistance compromising yield and quality, new agents are urgently needed. In this study, a series of novel arecoline derivatives incorporating a quinazolin moiety were synthesized, and the bioassay results demonstrated that these derivatives exhibited potent antifungal activity. Compound <b>1a</b> inhibited <i>C. camelliae</i> by 81.1% at 100 μg/mL in vitro (EC₅₀ = 5.285 μg/mL), outperforming azoxystrobin (71.1%). Detached leaf assays confirmed 100% in vivo control at this concentration. Mechanistically, it disrupted fungal membranes; induced hyphal abnormalities; upregulated tea plant defense enzymes (CAT, POD, and SOD); and modulated jasmonic/salicylic acid pathways, metabolism, and oxidative responses (omics analyses). This study not only expands the application scope of the natural product quinazolin but also provides promising lead compounds for the development of eco-friendly fungicides in tea plant protection.