Novel tryptamine derivatives incorporating aromatic aldehyde and amide moieties: design, synthesis, and antifungal activity

Abstract BACKGROUND Fungus Podosphaera xanthii (syn. Sphaerotheca fuliginea ) can cause cucurbit powdery mildew, posing a serious threat to cucurbit production. Chemical control is widely preferred for managing powdery mildew on cucurbits. A series of novel tryptamine derivatives were designed and synthesized, and their curative activity against Podosphaera xanthii was systematically evaluated using a whole‐plant bioassay. RESULTS In vivo activity assays of the tryptamine derivatives against P. xanthii revealed that 13h and 5o exhibited excellent curative effects, with median effective concentration (EC 50 ) values of 18.07 and 22.08 μg mL −1 , respectively, comparable to that of the positive control difenoconazole (EC 50 = 14.77 μg mL −1 ). Scanning electron microscopy (SEM) and Coomassie Brilliant Blue R‐250 staining demonstrated that compound 13h induced pronounced hyphal breakage, collapse and disintegration, along with pronounced curling. Additionally, transmission electron microscopy (TEM) observations confirmed that 13h compromised cellular integrity, leading to irreversible organelle damage and tissue disintegration, ultimately suppressing hyphal proliferation. CONCLUSION Structure–activity relationships (SARs) were established for a new type of tryptamine derivatives incorporating aromatic aldehyde and amide moieties, providing guidance for designing tryptamine‐based antifungal agents. Given the potent curative activity of compound 13h , it holds great promise as a novel antifungal agent. © 2026 Society of Chemical Industry.