title: Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold.
abstract: Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR,1H-NMR,13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein-1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein-1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC50values of compounds for esterase activity are in the range of 118.4 ± 7.0 μM-257.5 ± 5.2 μM for hCA I and 86.7 ± 3.0 μM-249.4 ± 10.2 μM for hCA II, respectively.
authors.affiliation: a Department of Chemistry and.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Ulus
authors.affiliation: b Department of Biochemistry , Faculty of Arts and Science, Dumlupinar University , Kütahya , Turkey.
authors.forename: Muharrem
authors.initials: M
authors.lastname: Kaya
authors.affiliation: a Department of Chemistry and.
authors.forename: Damla
authors.initials: D
authors.lastname: Demir
authors.affiliation: b Department of Biochemistry , Faculty of Arts and Science, Dumlupinar University , Kütahya , Turkey.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Tunca
authors.affiliation: b Department of Biochemistry , Faculty of Arts and Science, Dumlupinar University , Kütahya , Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; 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 / Q000737:chemistry / Q000494:pharmacology*; D002846:Chromatography, Affinity; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013414:Sulfaguanidine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C429843:1,2,3,4,5,6,7,8-octahydroacridine; D000166:Acridines; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013414:Sulfaguanidine; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Acridine; carbonic anhydrase; inhibition; sulfaguanidine