The effects of some bromophenols on human carbonic anhydrase isoenzymes

J Enzyme Inhib Med Chem. 2016 Aug;31(4):603-7. doi: 10.3109/14756366.2015.1054820. Epub 2015 Jul 2.

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1), which are involved in a variety of physiological and pathological processes, are ubiquitous metalloenzymes mainly catalyzing the reversible hydration of carbon dioxide (CO2) to bicarbonate ([Formula: see text]) and proton (H(+)). In this study, a dozen of bromophenol derivatives (1-12) were evaluated as metalloenzyme CA (EC 4.2.1.1) inhibitors against the human carbonic anhydrase isoenzymes I and II (hCA I and II). Cytosolic hCA I and II isoenzymes were effectively inhibited by bromophenol derivatives (1-12) with Kis in the low nanomolar range of 1.85 ± 0.58 to 5.04 ± 1.46 nM against hCA I and in the range of 2.01 ± 0.52 to 2.94 ± 1.31 nM against hCA II, respectively.

Keywords: Bromophenols; carbonic anhydrase; enzyme inhibition; enzyme purification; isoenzymes.

MeSH terms

  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Phenols
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II