title: Effects of dopaminergic compounds on carbonic anhydrase isozymes I, II, and VI.
abstract: Studies on carbonic anhydrase (CA, EC 4.2.1.1) inhibitors have increased due to several therapeutic applications while there are few investigations on activators. Here we investigated CA inhibitory and activatory capacities of a series of dopaminergic compounds on human carbonic anhydrase (hCA) isozymes I, II, and VI. 2-Amino-1,2,3,4-tetrahydronaphthalene-6,7-diol hydrobromide and 2-amino-1,2,3,4-tetrahydronaphthalene-5,6-diol hydrobromide were found to show effective inhibitory action on hCA I and II whereas 2-amino-5,6-dibromoindan hydrobromide and 2-amino-5-bromoindan hydrobromide exhibited only moderate inhibition against both isoforms, being more effective inhibitors of hCA VI. K(i) values of the molecules 3-6 were in the range of 41.12-363 μM against hCA I, of 0.381-470 μM against hCA II and of 0.578-1.152 μM against hCA VI, respectively. Compound 7 behaved as a CA activator with K(A) values of 27.3 μM against hCA I, of 18.4 μM against hCA II and of 8.73 μM against hCA VI, respectively.
authors.affiliation: Ağrı İbrahim Çeçen University, Science and Art Faculty, Chemistry Department, Ağrı, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sentürk
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.forename: Süleyman
authors.initials: S
authors.lastname: Göksu
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000097:blood / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D018492:Dopamine Antagonists; D007527:Isoenzymes; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI