Synthesis of 1,4-Bis(indolin Derivatives and Their Structure-Activity Relationships for the Interaction of Human Carbonic Anhydrase Isoforms I and II

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 K<inf>I</inf> values were calculated. K<inf>I</inf> values of compounds for hCA I and hCA II human isozymes were measured in the range of 39.3-42.6 μM and 0.17-0.29 μM, 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. © 2012 Elsevier Ltd. All rights reserved.