Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase

  • Bioorg Chem. 2019 Sep:90:103058. doi: 10.1016/j.bioorg.2019.103058.
Josephine M Gießel  1 ,  Immo Serbian  1 ,  Anne Loesche  1 ,  René Csuk  2
Affiliations
  • 1. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes Str. 2, D-06120 Halle (Saale), Germany.
  • 2. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes Str. 2, D-06120 Halle (Saale), Germany. Electronic address: [email protected].
PMID: 31212181 DOI: 10.1016/j.bioorg.2019.103058
Abstract

Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Ki = 8.30 ± 0.94 µM and Ki' = 9.54 ± 0.38 µM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Ki = 8.23 ± 0.93 µM and Ki' = 13.07 ± 0.46 µM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).

Keywords
Acetylcholinesterase; Butyrylcholinesterase; Cinnamic anhydrides; Inhibitors.
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