Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b] indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI

EKİNCİ D., ÇAVDAR H., Durdagi S., TALAZ O., ŞENTÜRK M., Supuran C. T.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.49, ss.68-73, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1016/j.ejmech.2011.12.022
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.68-73
  • Anahtar Kelimeler: Carbonic anhydrase, Phenol inhibitor, Sulfonamide inhibitor, Docking, Indole, THERAPEUTIC APPLICATIONS, INHIBITORS, ACTIVATORS, MELATONIN, ANTIOXIDANT, MOLECULE, COUMARINS, DOCKING, BINDING, ADDUCT
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

Several 5,10-dihydroindeno[1,2-b]indole derivatives incorporating methoxy, hydroxyl, and halogen (F, Cl, and Br) moieties on the indene fragment of the molecule were prepared and tested against five carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The inhibitory potencies of these compounds against the human (h) isoforms hCA I, II, IV, VI and bovine (b) isoform bCA III were assessed. Most of them exhibited low micromolar inhibition of these enzymes. K-I values of these compounds against hCA I and hCA II were in the range of 2.14-16.32 mu M, and 0.34-2.52 mu M, respectively. Isozyme hCA IV was inhibited with K-I-s in the range of 0.435-5.726 mu M, while hCA VI with K-I-s of 1.92-12.84 mu M bCA III was inhibited with K-I-s in the range of 2.13-17.83 mu M. The structurally related compounds, 1,2-dimethoxybenzene, catechol and indole were also tested in order to understand the structure activity relationship. In silico docking studies of some derivatives within the active site of hCA I and II were also carried out in order to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism. (C) 2011 Elsevier Masson SAS. All rights reserved.