title: Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors of human carbonic anhydrase isozymes (hCA-I and hCA-II).
abstract: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (3a--s) were designed as human carbonic anhydrase isozymes (hCA-I and hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of 18 newly synthesized acetophenones on hydratase activity of these isoenzymes were studied in vitro. The average IC50 values of the new compounds for hydratase activity ranged from 0.033 to 0.14 μM for hCA-I and from 0.030 to 0.11 μM for hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]-4'-bromoacetophenone (3n) can be considered as a promising hCA-II inhibitor owing to its selective and potent inhibitory effect on hCA-II.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University , Eskisehir , Turkey .
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altintop
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozdemir
authors.forename: Kaan
authors.initials: K
authors.lastname: Kucukoglu
authors.forename: Gulhan
authors.initials: G
authors.lastname: Turan-Zitouni
authors.forename: Hayrunnisa
authors.initials: H
authors.lastname: Nadaroglu
authors.forename: Zafer Asim
authors.initials: ZA
authors.lastname: Kaplancikli
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry*; D024401:Carbonic Anhydrase I / Q000737:chemistry* / Q000302:isolation & purification; D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000302:isolation & purification; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D002846:Chromatography, Affinity; D057075:Enzyme Assays; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000098:Acetophenones; D002257:Carbonic Anhydrase Inhibitors; D013830:Thiadiazoles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Carbonic anhydrase; hydratase activity; thiadiazole