title: Bile acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide as new carbonic anhydrase inhibitors: synthesis and investigation of inhibition effects.
abstract: Bile acid amides (cholan-24-amides) of 5-substituted 1,3,4-thiadiazole-2-sulfonamide have been prepared from lithocholic, deoxycholic, cholic and dehydrocholic acids. Besides, the alcohol functional groups on the cholane ring systems were protected with acetyl group. Amides of the protected cholanes of lithocholic and cholic acids were also synthesized. Later, inhibition effects of these compounds on human carbonic anhydrase isozymes (HCA-I and II) have been investigated in vitro. For the most active compounds, inhibition constants ranged from 66 to 190nM for HCA-II with I(50) (molarity of inhibitor producing a 50% inhibition of CA activity). In addition, in vivo studies were performed for the synthesized compounds in Sprague-Dawley rats. The compounds (11 and 18) showed especially significant inhibition efficacy (p<0.001).
authors.affiliation: Faculty of Science and Arts, Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
authors.forename: Nurullah
authors.initials: N
authors.lastname: Saraçoğlu
authors.forename: O Irfan
authors.initials: OI
authors.lastname: Küfrevioğlu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ciftçi
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007274:Injections, Intraperitoneal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013830:Thiadiazoles; C404727:5-amino-1,3,4-thiadiazole-2-sulfonamide; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II