Synthesis of 1,4-bis(indolin-1-ylmethyl)benzene derivatives and their structure-activity relationships for the interaction of human carbonic anhydrase isoforms I and II

Bioorg Med Chem. 2013 Mar 15;21(6):1477-82. doi: 10.1016/j.bmc.2012.09.027. Epub 2012 Oct 10.

Abstract

Several 1,4-bis(indolin-1-ylmethyl)benzene-based compounds containing substituents such as five, six and seven cyclic derivatives on indeno part (9a-c) were prepared and tested against two members of the pH regulatory enzyme family, carbonic anhydrase (CA). The inhibitory potencies of the compounds at the human isoforms hCA I and hCA II targets were analyzed and KI values were calculated. KI values of compounds for hCA I and hCA II human isozymes were measured in the range of 39.3-42.6μM and 0.17-0.29μM, respectively. The structurally related compound indole was also tested in order to understand the structure-activity relationship. Most of the compounds showed good CA inhibitory efficacy. In silico docking studies of these derivatives within hCA I and II were also carried out and results are supported the kinetic assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / metabolism
  • Binding Sites
  • 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 / metabolism
  • Catalytic Domain
  • Humans
  • Indoles / chemistry*
  • Kinetics
  • Molecular Docking Simulation
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Benzene Derivatives
  • Carbonic Anhydrase Inhibitors
  • Indoles
  • indoline
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II