A Phytotoxic Sulfonamide from a Colletotrichum graminicola Culture Extract and 116 Synthetic Analogues: A SAR Study

In a bioactivity-guided approach, phytotoxic compounds were isolated from culture extracts of the phytopathogenic fungus Colletotrichum graminicola, leading to the identification of N-(4-hydroxybutyl)-benzenesulfonamide (1). Initial derivatization of 1 resulted in enhanced activity, motivating a structure–activity relationship (SAR) study based on a library of 116 synthetic analogues and the parent compound 1. Phytotoxic effects were evaluated phenotypically using a leaf-spot assay on Arabidopsis thaliana Col-0 and a non-destructive leaf-disk assay based on delayed fluorescence. Exploratory SAR analysis indicated that physicochemical parameters such as molar mass (M), partition coefficient (log P), and the steric bulk of the substituents may contribute to the observed phytotoxic activity. Significant enhancement of phytotoxic activity was achieved through structural optimization. Several derivatives remained active at 0.4 mM, whereas the parent compound was inactive at 15 mM under the same assay conditions.