Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties

Arch Pharm (Weinheim). 2018 Nov;351(11):e1800209. doi: 10.1002/ardp.201800209. Epub 2018 Sep 26.

Abstract

Sulfamates have a large spectrum of biological activities including enzyme inhibition. Eight sulfamates derived from menthol (2a-h) were synthesized. Also, in the other section of this study, novel sulfamate derivatives of menthol were tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carbonic anhydrase I and II enzymes (hCAs I and II). The newly synthesized novel menthol sulfamate and menthol carbonyl sulfamate derivatives showed Ki values in the range of 34.37 ± 8.17 to 53.40 ± 10.61 nM against hCA I, 12.91 ± 4.57 to 38.67 ± 6.22 nM against hCA II, 111.17 ± 52.36 to 522.86 ± 120.08 nM against AChE, and 50.01 ± 11.73 to 109.63 ± 50.08 nM against BChE. As a result, the novel menthol sulfamate and menthol carbonyl sulfamate derivatives can be promising Alzheimer's disease drug candidates and novel hCA I and hCA II enzymes inhibitors.

Keywords: acetylcholinesterase; butyrylcholinesterase; carbonic anhydrase; enzyme inhibition; sulfamate.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Butyrylcholinesterase / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Menthol / chemistry*
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Sulfonic Acids
  • Menthol
  • sulfamic acid
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Carbonic Anhydrases

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