Derivative D37(Nanjing Agricultural University)

Streptochlorin, a marine indole alkaloid with broad‐spectrum bioactivity, has been structurally modified by introducing sulfonamide at the 3‐position of the indole scaffold to enhance its antifungal potential.

A series of sulfonamide‐containing derivatives were designed, synthesized, and evaluated against seven phytopathogenic fungi. Notably, derivatives D35 – D37 exhibited potent antifungal activity, demonstrating >60% inhibition against most tested fungi and > 85% efficacy against Valsa mali . Structure–activity relationship (SAR) analysis revealed that 3‐phenylsulfonamide substitution conferred optimal activity. Molecular docking studies suggested that these derivatives likely targeted the cytochrome bc1 complex, implicating fungal respiration disruption as a potential mode of action.

The 3‐phenylsulfonamide‐modified streptochlorin derivatives exhibited potent antifungal activity, with D35 ‐ D37 showing particular efficacy. Their successful synthesis offers a novel antifungal scaffold, while preliminary studies suggest potential cytochrome bc1 complex inhibition as a mode of action. © 2026 Society of Chemical Industry.