1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

Molecules. 2021 Jun 28;26(13):3942. doi: 10.3390/molecules26133942.

Abstract

A series of new analogs of nitrogen mustards (4a-4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman's colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively.

Keywords: 1,3,5-triazine; acetylcholinesterase; nitrogen mustards; β-secretase.

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Amyloid Precursor Protein Secretases* / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases* / chemistry
  • Aspartic Acid Endopeptidases* / antagonists & inhibitors
  • Aspartic Acid Endopeptidases* / chemistry
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • GPI-Linked Proteins / chemistry
  • Humans
  • Nitrogen Mustard Compounds* / chemical synthesis
  • Nitrogen Mustard Compounds* / chemistry
  • Peptides* / chemical synthesis
  • Peptides* / chemistry
  • Triazines* / chemical synthesis
  • Triazines* / chemistry

Substances

  • Cholinesterase Inhibitors
  • GPI-Linked Proteins
  • Nitrogen Mustard Compounds
  • Peptides
  • Triazines
  • ACHE protein, human
  • Acetylcholinesterase
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human