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

TALAZ O., ÇAVDAR H., Durdagi S., AZAK H., EKİNCİ D.

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.21, sa.6, ss.1477-1482, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 21 Sayı: 6
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.bmc.2012.09.027
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.1477-1482
  • Anahtar Kelimeler: Carbonic anhydrase, Docking, Bisindole, Glaucoma, SEA-BASS LIVER, VITRO INHIBITION, GLUTATHIONE-REDUCTASE, FISCHER INDOLIZATION, EFFICIENT SYNTHESIS, INDOLE-DERIVATIVES, ISOZYMES I, SULFONAMIDES, BINDING, ENZYME
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

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-I values were calculated. K-I values of compounds for hCA I and hCA II human isozymes were measured in the range of 39.3-42.6 mu M and 0.17-0.29 mu M, 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. (C) 2012 Elsevier Ltd. All rights reserved.