title: 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.
abstract: 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 μM, and 0.34-2.52 μM, respectively. Isozyme hCA IV was inhibited with K(I)-s in the range of 0.435-5.726 μM, while hCA VI with K(I)-s of 1.92-12.84 μM bCA III was inhibited with K(I)-s in the range of 2.13-17.83 μM. 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.
authors.affiliation: Ondokuz Mayıs University, Faculty of Agriculture, Department of Agricultural Biotechnology, Samsun, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Cavdar
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Oktay
authors.initials: O
authors.lastname: Talaz
authors.forename: Murat
authors.initials: M
authors.lastname: Sentürk
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D020033:Protein Isoforms / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007211:Indoles; D020033:Protein Isoforms; C057286:indenoindole; D002256:Carbonic Anhydrases