title: Synthesis and characterization of phenolic Mannich bases and effects of these compounds on human carbonic anhydrase isozymes I and II.
abstract: Mannich bases 2a-f derived from 3,4-dimethylphenol (1), formaldehyde and different amines are prepared and subjected to spectral (IR, (1)H and (13)C NMR) and elemental analyses. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with 1 and synthesized Mannich bases 2a-f and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. In relation to hydratase and esterase activities of the half maximal inhibitory concentration (IC(50)) and the inhibition equilibrium constants (K(i))values were determined. Only two compounds (2a and 2e)exhibit weak hCA II inhibitory effects on esterase activity. IC(50) and Ki values for 2a and 2e with respect to esterase activity of hCA II are0.88 × 10(3) and 6.3-7.6 µM and 0.44 × 10(3) and 19.0-96.4 µM,respectively. On the contrary, compounds 2b and 2d might be used as CA activators due to increasing esterase activity of hCA I and hCA II isozymes.
authors.affiliation: Department of Chemistry, Faculty of Arts and Science, Dumlupinar University, Kütahya, Turkey.
authors.forename: Nurgün
authors.initials: N
authors.lastname: Büyükkidan
authors.forename: Bülent
authors.initials: B
authors.lastname: Büyükkidan
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
authors.forename: Salih
authors.initials: S
authors.lastname: Özer
authors.forename: Hatice
authors.initials: H
authors.lastname: Gonca Yalçin
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D005557:Formaldehyde / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000588:Amines; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D014992:Xylenes; D005557:Formaldehyde; C063628:3,4-dimethylphenol; D002256:Carbonic Anhydrases