Evaluation of acetylcholinesterase and carbonic anhydrase inhibition profiles of 1,2,3,4,6-pentasubstituted-4-hydroxy-cyclohexanes

J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21938. Epub 2017 Jun 14.

Abstract

Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimer's disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE). These six-membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with Ki values in the range of 6.70-35.85 nM for hCA I, 18.77-60.84 nM for hCA II, and 0.74-4.60 for AChE, respectively.

Keywords: acetylcholinesterase; carbonic anhydrase; domino reactions; enzyme inhibition pentasubstituted cyclohexanol.

Publication types

  • Evaluation Study

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Carbonic Anhydrase I* / antagonists & inhibitors
  • Carbonic Anhydrase I* / chemistry
  • Carbonic Anhydrase II* / antagonists & inhibitors
  • Carbonic Anhydrase II* / chemistry
  • Carbonic Anhydrase Inhibitors* / chemical synthesis
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • Cyclohexanes* / chemical synthesis
  • Cyclohexanes* / chemistry
  • GPI-Linked Proteins / chemistry
  • Humans

Substances

  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Cyclohexanes
  • GPI-Linked Proteins
  • ACHE protein, human
  • Acetylcholinesterase
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II