An α,α-Dihalogenated Acetophenone Derivative: A Novel Antifungal Agent with a Dual-Targeting Mechanism against Colletotrichum gloeosporioides

The widespread application of commercial chemical fungicides has accelerated the evolution of fungicide resistance in Fungal pathogens, posing a significant threat to global food security and agricultural sustainability. Anthracnose, caused by Colletotrichum, is a devastating Fungal disease that leads to significant economic losses worldwide. The rising fungicide resistance of species of Colletotrichum highlights the need to develop novel fungicides. In this study, we identified that certain α,α-dihalogenated acetophenone derivatives exhibit potent Antifungal activity against C. gloeosporioides. Notably, compound Ii displayed exceptional inhibitory efficacy, effectively suppressing vegetative growth and pathogenicity at a low concentration of 18 μg·mL^-1. Using a T-DNA insertional mutant library, we identified two genes, CgSFU1 and CgRIDA, which play distinct roles in the response to compound Ii. Deletion of CgSFU1 enhanced sensitivity to compound Ii, while disruption of CgRIDA conferred resistance to compound Ii in C. gloeosporioides. Molecular docking analysis revealed that compound Ii binds to CgRidA at the TRP-40 or TYR-22 residues through hydrophilic interactions, thereby disrupting its regulatory functions. These findings provide insights into how C. gloeosporioides responds to compound Ii in two distinct manners and highlight its potential as a novel Antifungal agent targeting Fungal regulatory proteins.

CgRIDA; CgSFU1; Colletotrichum; molecular docking; α,α-dihalogenated acetophenone.