Design, Synthesis, and Fungicidal Activity against Rice Sheath Blight of Novel N-Acyl-1,2,3,4-tetrahydroquinoline Derivatives

To discover fungicides with novel targets, a series of N-acyl-1,2,3,4-tetrahydroquinoline (NATHQ) derivatives weredesigned and synthesized by linking the active substructure NATHQmoiety in aspernigerin with the O-benzyl oxime-etherscaffold in commercial agrochemicals. Target compound structures wereidentified using proton and carbon-13 nuclear magnetic resonance spectroscopiesand high-resolution mass spectrometry. Preliminary bioassays indicatedthat at 40 mg/L, some target compounds exhibited moderate to considerablein vitro fungicidal activities against Rhizoctoniasolani and Botrytis cinerea. In particular, compound 3j exhibited higher fungicidalactivities 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 bea 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-ethermoiety of compound 3j exhibited an excellent bindingmode with the laccase target protein and could be used as a lead compoundfor developing laccase inhibitors. The structural features of theseNATHQ derivatives will provide inspiration for developing laccaseinhibitors and discovering more effective fungicides to control agriculturaldiseases.