Bioorganic & Medicinal Chemistry 2013-03-15

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.

Oktay Talaz, Hüseyin Cavdar, Serdar Durdagi, Hacer Azak, Deniz Ekinci

文献索引：Bioorg. Med. Chem. 21(6) , 1477-82, (2013)

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摘要

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.Copyright © 2012 Elsevier Ltd. All rights reserved.