Non-competitive inhibition of acetylcholinesterase by bromotyrosine alkaloids

Nat Prod Commun. 2014 Nov;9(11):1559-61.

Abstract

Fifteen bromotyrosine-derived alkaloids were isolated from the sponge Pseudoceratina cf. purpurea. The acetylcholinesterase-inhibiting activity of all the isolated compounds were examined; to purealidin Q, isoanomoian A, aplyzanzine A, and aplysamine 2 were active with IC50 values of 1.2, 70, 104, and 1.3 μM, respectively. On the other hand, antiproliferative activity against MCF-7 cells of aerophobin 1 gave an IC50 value of 0.8 μM. The Michaelis-Menten plots of the active alkaloids indicated that all the four compounds inhibited acetylcholinesterase in a non-competitive manner. The structures of the active compounds suggested that the N,N-dimethylaminopropyloxydibromotyramine moiety may play an important role in the enzyme-inhibiting activity, presumably on the anionic and hydrophobic binding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Alkaloids / chemistry*
  • Alkaloids / pharmacology*
  • Cell Proliferation / drug effects
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology
  • Enzyme Activation / drug effects
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry
  • Tyrosine / pharmacology

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • aplysamine-2
  • bromotyrosine
  • Tyrosine
  • Acetylcholinesterase