Abstract

Gray mold (Botrytis cinerea) and brown rot (Monilinia fructicola) are devastating diseases in stone fruit production. In this work, a series of 3-acyl-6-bromoindoles, including six new compounds, were synthesized via green and efficient microwave-assisted methodology to evaluate their antifungal potential. Bioassays revealed a remarkable duality in the compounds’ mechanism of action. The starting material, 6-bromoindole (I), proved to be a highly potent inhibitor of mycelial growth, with a remarkable EC50 of 11.62 µg/mL against B. cinerea and 18.84 µg/mL against M. fructicola, surpassing BC-1000® and Captan® and comparable to Mystic®. Conversely, compound I was ineffective at inhibiting conidial germination. In stark contrast, the simple acetylated derivative 3-acetyl-6-bromoindole (II) emerged as a formidable inhibitor of spore germination, achieving 100% inhibition for B. cinerea and 96% for M. fructicola, outperforming several controls. This suggests that, while compound I is effective against established infections, compound II acts as a powerful preventative agent against initial spore-based propagation. The antifungal activity of the compounds directly correlates with their ability to bind to the enzymes SDH and MfCat2, the latter being the main mechanism of action. These findings highlight the potential of developing specialized fungicides from the 6-bromoindole scaffold, targeting different stages of fungal development.