Streptochlorin-derived sulfonamides: discovery of novel antifungal scaffold through structural modification and SAR analysis.

BACKGROUND

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.

RESULTS

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.

CONCLUSION

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.