Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.
Diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide, and bumetanide containing primary sulfamoyl moieties were reevaluated as inhibitors of 12 human carbonic anhydrases (hCAs, EC 4.2.1.1). These drugs considerably inhibit (low nanomolar range) some CA isozymes involved in critical physiologic processes, among the 16 present in vertebrates, for example, metolazone against CA VII, XII, and XIII, chlorthalidone against CA VB, VII, IX, XII, and XIII, indapamide against CA VII, IX, XII, and XIII, furosemide against CA I, II, and XIV, and bumetanide against CA IX and XII. The X-ray crystal structure of the hCA II-indapamide adduct was also resolved at high resolution.
Temperini
Claudia
C
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Room 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Cecchi
Alessandro
A
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D007190:Indapamide / Q000737:chemistry*; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases; D007190:Indapamide