Discovery of Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors: 2-Aminoindan β-Lactam Derivatives

Int J Mol Sci. 2016 Oct 20;17(10):1736. doi: 10.3390/ijms17101736.

Abstract

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The Ki values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both carbonic anhydrases (CA) isoenzymes and AChE at low nanomolar concentrations.

Keywords: 2-azetidinone; acetylcholinesterase; carbonic anhydrase; enzyme inhibition; enzyme purification; β-lactam.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase / metabolism*
  • Azetidines / chemistry
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrases / metabolism*
  • Cholinesterase Inhibitors / chemistry*
  • Humans
  • Indans / chemistry
  • Neurotransmitter Agents / metabolism
  • beta-Lactams / chemistry*

Substances

  • 2-azetidinone
  • Azetidines
  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Indans
  • Neurotransmitter Agents
  • beta-Lactams
  • 2-aminoindan
  • Acetylcholinesterase
  • Carbonic Anhydrases
  • Acetylcholine