New AChE inhibitors from microbial transformation of trachyloban-19-oic acid by Syncephalastrum racemosum

Bioorg Chem. 2018 Sep:79:60-63. doi: 10.1016/j.bioorg.2018.04.011. Epub 2018 Apr 16.

Abstract

Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2-3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1-4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimer's disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50 = 0.06 μM, which is about six times higher than activity found for galanthamine (IC50 = 0.38 μM), the positive control used in this assay.

Keywords: Acetylcholinesterase; Alzheimer’s disease; Biotransformation; Syncephalastrum racemosum; Trachyloban-19-oic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Biotransformation
  • Cholinesterase Inhibitors / chemistry*
  • Diterpenes / chemistry*
  • Diterpenes / metabolism*
  • Electrophorus
  • Enzyme Assays
  • Fruit / chemistry
  • Molecular Structure
  • Mucorales / metabolism*
  • Oxidation-Reduction
  • Xylopia / chemistry

Substances

  • Cholinesterase Inhibitors
  • Diterpenes
  • trachyloban-19-oic acid
  • Acetylcholinesterase