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

The detoxification of the phytoalexin brassinin to indole-3-carboxaldehyde and -methyl dithiocarbamate is catalyzed by brassinin oxidase (BOLm), an inducible fungal enzyme produced by the plant pathogen . Twenty-six substituted quinolines and isoquinolines are synthesized and evaluated for antifungal activity against and inhibition of BOLm. Eleven compounds that inhibit BOLm activity are reported, of which 3-ethyl-6-phenylquinoline displays the highest inhibitory effect.

Metabolism and metabolites of dithiocarbamates in the plant pathogenic fungus Leptosphaeria maculans.

Synthetic compounds containing a dithiocarbamate group are known to have a variety of biological effects and applications including antifungal, herbicidal, and insecticidal application. Leptosphaeria maculans is a fungal pathogen of crucifers able to detoxify efficiently the only plant natural product containing a dithiocarbamate group, the phytoalexin brassinin. To evaluate the effects of dithiocarbamates on L.

The cruciferous phytoalexins rapalexin A, brussalexin A and erucalexin: chemistry and metabolism in Leptosphaeria maculans.

The interactions of the cruciferous phytoalexins rapalexin A (1), brussalexin A (2) and erucalexin (3) with the fungal plant pathogen Leptosphaeria maculans were analyzed and their inhibitory activities against this pathogen were determined. The reaction of L. maculans to N-methyl S-(indolyl-3-methyl)carbamodithioate, an analogue of brussalexin A, was also investigated.

Brassinin oxidase mediated transformation of the phytoalexin brassinin: structure of the elusive co-product, deuterium isotope effect and stereoselectivity.

Brassinin oxidase, a fungal detoxifying enzyme that mediates the conversion of the phytoalexin brassinin into indole-3-carboxaldehyde, is the first enzyme described to date that catalyzes the transformation of a dithiocarbamate group into an aldehyde equivalent. Brassinin is an essential phytoalexin due to its antifungal activity and its role as biosynthetic precursor of other phytoalexins produced in plants of the family Brassicaceae (common name crucifer). In this report, the isolation, structure determination and synthesis of the elusive co-product of brassinin transformation by brassinin oxidase, S-methyl dithiocarbamate, the syntheses of dideuterated and (R) and (S) monodeuterated brassinins, kinetic analyses of isotope effects and chemical modifications of brassinin oxidase are described.

Discovery of inhibitors of brassinin oxidase based on the scaffolds of the phytoalexins brassilexin and wasalexin.

Inhibitors of brassinin oxidase (BOLm), a unique phytoalexin detoxifying enzyme produced by the plant pathogenic fungus Leptosphaeria maculans (asexual stage Phoma lingam), were designed based on scaffolds of the phytoalexins brassilexin and wasalexin. Evaluation of these compounds using purified BOLm established that the inhibitory effect of brassilexin and derivatives decreased as follows: 6-chlorobrassilexin approximately 6-bromobrassilexin>5-bromobrassilexin approximately 5-chlorobrassilexin approximately 6-fluorobrassilexin>8-methylbrassilexin>brassilexin approximately 5-fluorobrassilexin. 6-Chlorobrassilexin was determined to be the best competitive inhibitor of BOLm discovered to date, with a K(i)=31microM.

Substrate specificity and inhibition of brassinin hydrolases, detoxifying enzymes from the plant pathogens Leptosphaeria maculans and Alternaria brassicicola.

Blackleg (Leptosphaeria maculans and Leptosphaeria biglobosa) and black spot (Alternaria brassicicola) fungi are devastating plant pathogens known to detoxify the plant defence metabolite, brassinin. The significant roles of brassinin as a crucifer phytoalexin and as a biosynthetic precursor of several other plant defences make it important in plant fitness. Brassinin detoxifying enzymes produced by L.

Synthetic inhibitors of the fungal detoxifying enzyme brassinin oxidase based on the phytoalexin camalexin scaffold.

Brassinin (1) is an essential phytoalexin produced in plants of the family Brassicaceae (common name crucifer) due to its role as a biosynthetic precursor of other phytoalexins and antimicrobial activity. The dithiocarbamate group of brassinin (1) is the toxophore responsible for its fairly broad antifungal activity. To the detriment of many agriculturally important crops, several pathogenic fungi of crucifers are able to overcome brassinin by detoxification.

Detoxification of the phytoalexin brassinin by isolates of Leptosphaeria maculans pathogenic on brown mustard involves an inducible hydrolase.

Brassinin is a phytoalexin produced by plants from the family Brassicaceae that displays antifungal activity against a number of pathogens of Brassica species, including Leptosphaeria maculans (Desm.) Ces. et de Not.