Design, synthesis and antifungal study of novel 2-aryl-3,4-dihydroisoquinolin-2-ium salts containing benzoate moieties

Abstract

To discover natural-derived fungicides, three series of 2-aryl-3,4-dihydroisoquinolinium salts (6–8) containing benzoate moieties were designed and synthesized based-on quaternary isoquinoline alkaloids. Their structures were confirmed by spectroscopic analysis. Antifungal activities against 10 phytopathogenic fungi were evaluated in vitro at 50 mg/L. Most of the title compounds exhibited moderate to excellent fungicidal activities, which were as active as the positive controls (chlorothalonil, carbendazim) and better than the reference model 9. Furthermore, for R. solani and R. cerealis 8c presented EC₅₀ values of 5.03 and 7.41 mg/L, respectively, equal to or superior than chlorothalonil (4.63 mg/L, 15.0313 mg/L). The SARs studies indicated that introduce the benzoate moieties had significant effect on the antifungal activity, in which the presence of 3′-CO₂Me (7) and 4′-CO₂Me (8) derivatives were more active than 2′-CO₂Me ones (6). Further mechanism studies on R. solani elucidated that compound 8c could increase the permeability of the cell membrane, dramatically induce the accumulation of ROS. These results revealed that compound 8c could represent as a potential lead for the development of antifungal agents.