To discover fungicides with novel targets, a series of N-acyl-1,2,3,4-tetrahydroquinoline (NATHQ) derivatives were designed and synthesized by linking the active substructure NATHQ moiety in aspernigerin with the O-benzyl oxime-ether scaffold in commercial agrochemicals. Target compound structures were identified using proton and carbon-13 nuclear magnetic resonance spectroscopies and high-resolution mass spectrometry. Preliminary bioassays indicated that at 40 mg/L, some target compounds exhibited moderate to considerable in vitro fungicidal activities against Rhizoctonia solani and Botrytis cinerea. In particular, compound 3j exhibited higher fungicidal activities both in vitro (EC50 = 0.733 mg/L) and in vivo (EC50 = 15.2 mg/L) against R. solani than the commercial fungicide prochloraz; therefore, it should be a promising fungicide candidate against rice sheath blight. Additionally, compound 3j exhibited good laccase inhibitory activity (73.2% at 200 mg/L). Molecular docking revealed that the bis-cyano-oxime-ether moiety of compound 3j exhibited an excellent binding mode with the laccase target protein and could be used as a lead compound for developing laccase inhibitors. The structural features of these NATHQ derivatives will provide inspiration for developing laccase inhibitors and discovering more effective fungicides to control agricultural diseases.
Keywords: N-acyl-1,2,3,4-tetrahydroquinoline derivatives; fungicidal activity; laccase inhibitors; oxime-ether derivatives; rice sheath blight.