Identification of Novel Anthrax Lethal Factor Inhibitors Generated by Combinatorial Pictet–Spengler Reaction Followed by Screening in situ

Abstract

Potent library. Anthrax lethal factor (LF) is a zinc-dependent metalloprotease involved in the rapid development of the deadly infection caused by Bacillus anthracis. Blocking its action is a plausible method to mitigate the deleterious effects of late stage infection. We report the inhibition of LF by tetrahydro-isoquinoline polyphenolic compounds, such as 5 a, which were identified by screening a combinatorial library that was generated by Pictet–Spengler reaction. We also report the identification of commercially available polyphenolic inhibitors against LF. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2005/z500009_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.