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Design, synthesis, and evaluation of potential inhibitors of brassinin glucosyltransferase, a phytoalexin detoxifying enzyme fromSclerotinia sclerotiorum

Authors
Journal
Bioorganic & Medicinal Chemistry
0968-0896
Publisher
Elsevier
Publication Date
Volume
15
Issue
17
Identifiers
DOI: 10.1016/j.bmc.2007.05.072
Keywords
  • Brassinin
  • Sclerotinia Sclerotiorum
  • Detoxifying Enzyme
  • Brassinin Glucosyltransferase
  • Phytoalexin
  • Dithiocarbamate
  • Antifungal
  • Paldoxin
Disciplines
  • Design

Abstract

Abstract Sclerotinia sclerotiorum is a fungal pathogen, which causes stem rot in crucifer crops and in several other plant families resulting in enormous yield losses all over the world. Brassinin is a phytoalexin produced by crucifer plants as part of a general defense mechanism against pathogens and other forms of stress. To the great detriment of crucifers, some fungal pathogens, as for example S. sclerotiorum, can detoxify brassinin. Detoxification of brassinin via glucosylation of the indole nitrogen is carried out by an inducible glucosyltransferase produced in S. sclerotiorum. Because brassinin is a precursor of several phytoalexins active against S. sclerotiorum, brassinin glucosyltransferase (BGT) is a potentially useful metabolic target to control S. sclerotiorum. Toward this end, we have designed, synthesized, and screened several brassinin analogues using both mycelial cultures and cell-free homogenates of S. sclerotiorum. A noticeable decrease in the rate of brassinin detoxification in cell cultures was observed in the presence of methyl (benzofuran-3-yl)methyldithiocarbamate, methyl (benzofuran-2-yl)methyldithiocarbamate, methyl (indol-2-yl)methyldithiocarbamate, 3-phenylindole, 6-fluoro-3-phenylindole, and 5-fluorocamalexin. In addition, these compounds caused substantial inhibition of BGT activity (ca. 80%) in cell-free homogenates of S. sclerotiorum, while only brassinin and 3-phenylindole were transformed to the corresponding β- d-1-glucopyranosyl products. These results indicate that, although many other glucosyltransferases appear to be produced by S. sclerotiorum in cell cultures, BGT is substrate specific. Overall these results show that selective and potent inhibitors of BGT can be developed.

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