title: Synthesis and carbonic anhydrase isoenzymes inhibitory effects of brominated diphenylmethanone and its derivatives.
abstract: Known and novel derivatives including CO, Br, and OH (benzylic and phenolic), and the corresponding benzylic alcohols of (3,4-dimethoxyphenyl)(2,3,4-dimethoxyphenyl)methanone were synthesized, and their inhibitory effects on the carbonic anhydrase (CA) isoenzymes I and II were investigated. CAs are the metalloenzymes catalyzing the reversible hydration of carbon dioxide (CO2 ) to bicarbonate (HCO3 (-) ). The inhibitory effects of diphenylmethanone derivatives 5-18 were tested on human CA (hCA, EC 4.2.1.1) isoenzymes (hCA I and hCA II) and they inhibited both isoenzymes at micromolar levels. Compounds 5 and 10 were found to be the best inhibitors against both CA isoenzymes. According to our data, compound 10 was the best inhibitor for isoenzyme hCA I (IC50  = 3.48 µM, Ki  = 2.19 µM) whereas compound 5 was found to be the best inhibitor for isoenzyme hCA II (IC50  = 1.33 µM, Ki  = 2.09 µM). Probably, stable conformations of 5 and 10 are more convenient for interaction with CA isoenzymes than those of the other compounds.
authors.affiliation: Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey; Department of Food Technology, Oltu Vocational School, Atatürk University, Oltu-Erzurum, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Çetinkaya
authors.forename: Hülya
authors.initials: H
authors.lastname: Göçer
authors.forename: Ilhami
authors.initials: I
authors.lastname: Gülçin
authors.forename: Abdullah
authors.initials: A
authors.lastname: Menzek
mesh_terms: D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007527:Isoenzymes; D015394:Molecular Structure
chemical_list: D001577:Benzophenones; D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D006842:Hydrocarbons, Brominated; D007527:Isoenzymes; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Benzylalcohol; Bromination; Carbonic anhydrase; Enzyme inhibition; Reduction