Inhibition of human carbonic anhydrase isozymes I, II and VI with a series of bisphenol, methoxy and bromophenol compounds

J Enzyme Inhib Med Chem. 2012 Aug;27(4):467-75. doi: 10.3109/14756366.2011.596836. Epub 2011 Aug 4.

Abstract

Carbonic anhydrase inhibitors (CAI) are valuable molecules as they have several therapeutic applications, including anti-glaucoma activity. In this study, inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and VI with a series of bisphenol and bromophenol derivatives was investigated. Molecular docking studies of a set of such inhibitors within CA I and II were also performed. K(I) values of the molecules 2-9 were in the range of 10.025-892.109 μM for hCA I, 1.437-59.107 μM for hCA II and 11.143-919.182 μM for hCA VI, respectively. Reported inhibitory activities of molecules 2-9 will assist in better understanding of structure-activity relationship studies of CAI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Carbonic Anhydrase Inhibitors
  • Phenols
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrase IV
  • CA4 protein, human