Examination of α-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid. Issue 22 (15th November 2017)

• Record Type: Journal Article
• Authors: Xue, Song; Seki, Hajime; Remes, Marek; Šilhár, Peter; Janda, Kim
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 22(2017)
• Page Start: 4956
• Page End: 4959
• Publication Date: 2017-11-15
• Subjects: Botulinum neurotoxins -- Chicoric acid -- Structure-activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.10.021
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Botulinum neurotoxins (BoNT) are among the most toxic known substances and currently there are no effective treatments for intraneuronal BoNT intoxication. Chicoric acid (ChA) was previously reported as a BoNT/A inhibitor that binds to the enzyme's α-exosite. Herein, we report the synthesis and structure-activity relationships (SARs) of a series of ChA derivatives, which revealed essential binding interactions between ChA and BoNT/A. Moreover, several ChA-based inhibitors with improved potency against the BoNT/A were discovered.