Design, synthesis, and mechanism study of novel natural-based isoquinolone derivatives as potential antifungal agents

A series of isoquinolone compounds Ia-Iq containing amide moiety were rationally designed and synthesized based-on isoquinolone alkaloids. Their structures were confirmed by ¹H NMR,¹³C NMR and HRMS. Most of the title compounds showed medium to excellent antifungal activity in vitro at 50 mg/L. Especially, the EC₅₀ of Im (13.155 mg/L) against P. piricola was slightly better than chlorothalonil (14.323 mg/L). The in vivo activity of Im against P. piricola on apples was comparable to chlorothalonil. Preliminary mechanistic exploration illustrated that Im strongly damage the mycelium morphology. Furthermore, molecular electrostatic potential and molecular docking analysis revealed that Im could interact with the residues of SDH via hydrogen bond.