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

作者：Pedras M Soledade C^*; Minic Zoran; Sarma Mamillapalle Vijay K; Suchy Mojmir

来源：Bioorganic & Medicinal Chemistry, 2010, 18(7): 2456-2463.

DOI：10.1016/j.bmc.2010.02.054

• Brassinin
• Brassinin oxidase
• Brassilexin
• Cyclobrassinin
• Detoxification
• Leptosphaeria maculans
• Phoma lingam
• Paldoxin
• Phytoalexin
• Wasalexin A

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 approximate to 6-bromobrassilexin > 5-bromobrassilexin approximate to 5-chlorobrassilexin approximate to 6-fluorobrassilexin > 8-methylbrassilexin > brassilexin approximate to 5-fluorobrassilexin. 6-Chlorobrassilexin was determined to be the best competitive inhibitor of BOLm discovered to date, with a K-i = 31 mu M. Importantly, brassilexin and derivatives did not appear to induce BOLm in fungal cultures. Overall, these results suggest that the brassilexin scaffold is a good lead for further development of paldoxins against L. maculans, as it inhibits competitively BOLm without apparent induction.

• 出版日期2010-4