Inhibitors of the Detoxifying Enzyme of the Phytoalexin Brassinin Based on Quinoline and Isoquinoline Scaffolds

Abstract

The detoxification of the phytoalexin brassinin to indole-3-carboxaldehyde and <i>S</i>-methyl dithiocarbamate is catalyzed by brassinin oxidase (BOLm), an inducible fungal enzyme produced by the plant pathogen <i>Leptosphaeria maculans</i>. Twenty-six substituted quinolines and isoquinolines are synthesized and evaluated for antifungal activity against <i>L. maculans</i> and inhibition of BOLm. Eleven compounds that inhibit BOLm activity are reported, of which 3-ethyl-6-phenylquinoline displays the highest inhibitory effect. In general, substituted 3-phenylquinolines show significantly higher inhibitory activities than the corresponding 2-phenylquinolines. Overall, these results indicate that the quinoline scaffold is a good lead to design paldoxins (phytoalexin detoxification inhibitors) that inhibit the detoxification of brassinin by <i>L. maculans</i>.