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Titolo:
Carbonic anhydrase inhibitors and their therapeutic potential
Autore:
Supuran, CT; Scozzafava, A;
Indirizzi:
Univ Florence, Lab Chim Inorgan & Bioinorgan, I-50121 Florence, Italy UnivFlorence Florence Italy I-50121 Bioinorgan, I-50121 Florence, Italy
Titolo Testata:
EXPERT OPINION ON THERAPEUTIC PATENTS
fascicolo: 5, volume: 10, anno: 2000,
pagine: 575 - 600
SICI:
1354-3776(200005)10:5<575:CAIATT>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; LOWERING AROMATIC/HETEROCYCLIC SULFONAMIDES; ACUTE MOUNTAIN-SICKNESS; CEREBRAL BLOOD-FLOW; AQUEOUS-HUMOR FLOW; ISOZYME-II; DORZOLAMIDE HYDROCHLORIDE; GASTROINTESTINAL-TRACT; RETINITIS-PIGMENTOSA; MACULAR EDEMA;
Keywords:
antiglaucoma drugs; anti-ulcer drugs; carbonic anhydrase; cerebrovasodilators; diagnostic tools; diuretics; enzyme activator; epilepsy; isozymes I-XIV; macular oedema; neurological disorders; osteoporosis; sulphonamide; tumour growth inhibition;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
165
Recensione:
Indirizzi per estratti:
Indirizzo: Supuran, CT Univ Florence, Lab Chim Inorgan & Bioinorgan, Via Gino Capponi7, I-50121 Florence, Italy Univ Florence Via Gino Capponi 7 Florence Italy I-50121 Italy
Citazione:
C.T. Supuran e A. Scozzafava, "Carbonic anhydrase inhibitors and their therapeutic potential", EXPERT OP T, 10(5), 2000, pp. 575-600

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread zinc enzymes, present in archaeo- and eubacteria, algae, green plants and animals. Within theseorganisms CAs are encoded by three distinct, evolutionarily unrelated genefamilies: the alpha-CA, the beta-CA and the gamma-CA families, respectively. These enzymes are very efficient catalysts for the reversible hydration of CO2 to bicarbonate; the alpha-CAs possess high versatility, being able to catalyse other hydrolytic processes. It is not known whether other reactions catalysed by CAs (than the hydration of CO2/dehydration of HCO3-) may have physiological relevance in systems where these enzymes are present. CAsare inhibited primarily by two main classes of compounds: the metal complexing inorganic anions (e.g., cyanide, cyanate, thiocyanate, azide, hydrogensulphide etc.) and the unsubstituted sulphonamides possessing the general formula RSO2NH2 (R = aryl; hetaryl; perhaloalkyl). The first type of inhibitor was important for understanding in detail the catalytic and inhibitory mechanisms, whereas the second led to the development of several classes of pharmacological agents. Inhibitors of both types directly bind to the metalion within the enzyme active site, either by substituting the zinc-bound H2O/OH-, or adding to the co-ordination sphere, leading thus to pentaco-ordinated Zn(II). Sulphonamide CA inhibitors (CAIs) are useful as diuretics, orin the treatment and prevention of a variety of diseases such as glaucoma,epilepsy, congestive heart failure, mountain sickness, gastric and duodenal ulcers, neurological disorders and osteoporosis among others, as well as diagnostic tools. Their applications are due to the wide distribution of the different alpha-CA isozymes (14 are presently known) in higher vertebrates, where they play important physiological functions related to respirationand transport of CO2/HCO3 between metabolising tissues and the lungs, pH and CO2 homeostasis, electrolyte secretion in a variety of tissues/organs, and biosynthetic reactions, such as gluconeogenesis and ureagenesis, among others. CA activators have recently been described and their mechanism of action at molecular level elucidated. Such agents might be useful for developing therapies for the CA deficiency syndrome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 06:31:02