title: 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.
abstract: 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.
authors.affiliation: Karamanoğlu Mehmetbey University, Kamil Özdağ Science Faculty, Chemistry Department, 70100 Karaman, Turkey. otalaz@kmu.edu.tr
authors.forename: Oktay
authors.initials: O
authors.lastname: Talaz
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Cavdar
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Hacer
authors.initials: H
authors.lastname: Azak
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D001555:Benzene Derivatives; D002257:Carbonic Anhydrase Inhibitors; D007211:Indoles; C057812:indoline; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II