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
Yükleniyor...
Tarih
2012
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier France - Editions Scientifiques Medicales Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
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.
Açıklama
WOS:000302033300006
PubMed:22245047
PubMed:22245047
Anahtar Kelimeler
Carbonic Anhydrase, Phenol Inhibitor, Sulfonamide Inhibitor, Docking, Indole
Kaynak
WoS Q Değeri
Q1
Scopus Q Değeri
Cilt
49
Sayı
Künye
Ekinci, D., Çavdar, H., Durdağı, S., Talaz, O., Şentürk, M., Supuran, C. T. (2012). Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-<b>b</b>]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI. European Journal of Medicinal Chemistry, 49, 68-73.
