Genomes and Genes
carbonic anhydrase inhibitors
Summary: A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.
- Neri D, Supuran C. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10:767-77 pubmed publisher..These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy. ..
- Genead M, McAnany J, Fishman G. Topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia. Retina. 2012;32:826-33 pubmed publisher..To determine the value of a topical carbonic anhydrase inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema...
- Carta F, Scozzafava A, Supuran C. Sulfonamides: a patent review (2008 - 2012). Expert Opin Ther Pat. 2012;22:747-58 pubmed publisher..This privileged structural motif is likely to be present in other drugs in the future. ..
- Ikeda Y, Hisatomi T, Yoshida N, Notomi S, Murakami Y, Enaida H, et al. The clinical efficacy of a topical dorzolamide in the management of cystoid macular edema in patients with retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2012;250:809-14 pubmed publisher..The results demonstrated that a topical dorzolamide is effective for the treatment of CME in patients with RP, and that the positive treatment effects last for up to 6 months. ..
- Agrawal V, Bano S, Supuran C, Khadikar P. QSAR study on carbonic anhydrase inhibitors: aromatic/heterocyclic sulfonamides containing 8-quinoline-sulfonyl moieties, with topical activity as antiglaucoma agents. Eur J Med Chem. 2004;39:593-600 pubmed..Excellent results are obtained against all the three isozymes; CA I, II and IV of the zinc enzyme CA by using indicator parameters along with (1)chi(v). ..
- Innocenti A, Winum J, Hall R, Muhlschlegel F, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the fungal beta-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids. Bioorg Med Chem Lett. 2009;19:2642-5 pubmed publisher..The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs. ..
- Venance S, Cannon S, Fialho D, Fontaine B, Hanna M, Ptacek L, et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129:8-17 pubmed..Moreover, understanding the skeletal muscle channelopathies will hopefully lead to insights into the more common central nervous system channel diseases such as migraine and epilepsy...
- Chow T, Browne V, Heileson H, Wallace D, Anholm J, Green S. Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:296-301 pubmed..In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba. ..
- Supuran C. Carbonic anhydrases--an overview. Curr Pharm Des. 2008;14:603-14 pubmed..The presence of these ubiquitous enzymes in so many tissues and in so different isoforms, represents an attractive goal for the design of inhibitors or activators with biomedical applications. ..
- Mincione F, Scozzafava A, Supuran C. The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14:649-54 pubmed..Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease. ..
- Isik S, Kockar F, Arslan O, Guler O, Innocenti A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with anions. Bioorg Med Chem Lett. 2008;18:6327-31 pubmed publisher..8-55.6 mM) and strongly inhibited by bromide, iodide, and sulfamide (K(I)s of 8.7-10.8 microM). The other investigated anions showed inhibition constants in the low millimolar range...
- Supuran C. Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14:641-8 pubmed..Thus, these old drugs may be useful as leads for new applications. ..
- Genis C, Sippel K, Case N, Cao W, Avvaru B, Tartaglia L, et al. Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. Biochemistry. 2009;48:1322-31 pubmed publisher..This preliminary study demonstrates that the CA IX mimic may provide a useful model to design more isozyme-specific CA IX inhibitors, which may lead to development of new therapeutic treatments of some cancers. ..
- Steele R, Benedini F, Biondi S, Borghi V, Carzaniga L, Impagnatiello F, et al. Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma. Bioorg Med Chem Lett. 2009;19:6565-70 pubmed publisher..Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed ..
- Giacomotto J, Pertl C, Borrel C, Walter M, Bulst S, Johnsen B, et al. Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. Hum Mol Genet. 2009;18:4089-101 pubmed publisher..Two of the most active hits obtained were methazolamide and dichlorphenamide, carbonic anhydrase inhibitors widely used in human therapy. In C...
- Supuran C, Vullo D, Manole G, Casini A, Scozzafava A. Designing of novel carbonic anhydrase inhibitors and activators. Curr Med Chem Cardiovasc Hematol Agents. 2004;2:49-68 pubmed..e., CA I, II, III and IV. The possible physiologic relevance of CA activation will also be addressed, together with the recent pharmacological applications of blood CA isozymes activators, as potential memory enhancing drugs. ..
- Temperini C, Cecchi A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009;17:1214-21 pubmed publisher..The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications. ..
- Van Patot M, Leadbetter G, Keyes L, Maakestad K, Olson S, Hackett P. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008;9:289-93 pubmed publisher..Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting. ..
- Apushkin M, Fishman G, Grover S, Janowicz M. Rebound of cystoid macular edema with continued use of acetazolamide in patients with retinitis pigmentosa. Retina. 2007;27:1112-8 pubmed..Results from our study suggest that rebound of CME with the continued use of acetazolamide observed by OCT may occur more frequently than previously appreciated. ..
- Robertson N, Potter C, Harris A. Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion. Cancer Res. 2004;64:6160-5 pubmed..Thus, CAIX plays an important role in the growth and survival of tumor cells under normoxia and hypoxia, making it a potential target for cancer therapy, but is not involved in invasion. ..
- Innocenti A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of transmembrane isoforms IX, XII, and XIV with less investigated anions including trithiocarbonate and dithiocarbamate. Bioorg Med Chem Lett. 2010;20:1548-50 pubmed publisher..12-0.66mM). N,N-Diethyldithiocarbamate was a low micromolar inhibitor also against CA XII and XIV (K(I)s of 1.0-1.1microM), suggesting that this new zinc-binding group (CS2-) may lead to efficient inhibitors targeting transmembrane CAs...
- Innocenti A, Leewattanapasuk W, Muhlschlegel F, Mastrolorenzo A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the pathogenic yeast Candida glabrata with anions. Bioorg Med Chem Lett. 2009;19:4802-5 pubmed publisher..The other anions investigated showed inhibition constants in the low millimolar range, with the exception of bromide and iodide (K(I)s of 27-42 mM)...
- Fishman G, Apushkin M. Continued use of dorzolamide for the treatment of cystoid macular oedema in patients with retinitis pigmentosa. Br J Ophthalmol. 2007;91:743-5 pubmed..Results from this study suggest that patients with RP could potentially sustain a beneficial effect from continued treatment with a topical form of carbonic anhydrase inhibitor. ..
- Basnyat B, Gertsch J, Holck P, Johnson E, Luks A, Donham B, et al. Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. High Alt Med Biol. 2006;7:17-27 pubmed..02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m. ..
- Gugleta K. Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension. Curr Med Res Opin. 2010;26:1255-67 pubmed publisherDorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension...
- Feldman R, Tanna A, Gross R, Chuang A, Baker L, Reynolds A, et al. Comparison of the ocular hypotensive efficacy of adjunctive brimonidine 0.15% or brinzolamide 1% in combination with travoprost 0.004%. Ophthalmology. 2007;114:1248-54 pubmed..035). The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain. ..
- Aaslid R. Cerebral autoregulation and vasomotor reactivity. Front Neurol Neurosci. 2006;21:216-28 pubmed..In this chapter, the various CO2 and acetazolamide approaches that determine vasomotor reactivity are described and discussed. ..
- Grover S, Apushkin M, Fishman G. Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. Am J Ophthalmol. 2006;141:850-8 pubmed..We observed that some patients may show a "rebound phenomenon" with continued use of the medication; hence, there is a need for careful follow-up in patients being treated. ..
- Ran X, Wang H, Chen Y, Zeng Z, Zhou Q, Zheng R, et al. Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide. Heart Vessels. 2010;25:237-47 pubmed publisher..Our findings indicate a novel role for AQP1 in postnatal angiogenesis, which has implications in diverse pathophysiological conditions including wound healing, tumor metastasis, and organ regeneration...
- Pastorekova S, Zatovicova M, Pastorek J. Cancer-associated carbonic anhydrases and their inhibition. Curr Pharm Des. 2008;14:685-98 pubmed..This review summarizes research data related to distribution, regulation and functional aspects of CA IX and CA XII, and describes emerging possibilities for clinical exploitation of CA inhibitors as imaging tools and anticancer drugs. ..
- Liu J, Medeiros F, Slight J, Weinreb R. Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy. Ophthalmology. 2009;116:449-54 pubmed publisher..To compare the diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure (IOP) in patients already receiving monotherapy with latanoprost...
- Tricarico D, Mele A, Conte Camerino D. Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. Neuromuscul Disord. 2006;16:39-45 pubmed..The activation of Ca2+-activated-K+ channel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in K+ -deficient rats and in familial hypokalaemic-PP. ..
- Li Y, Wang H, Oosterwijk E, Tu C, Shiverick K, Silverman D, et al. Expression and activity of carbonic anhydrase IX is associated with metabolic dysfunction in MDA-MB-231 breast cancer cells. Cancer Invest. 2009;27:613-23 pubmed publisher..Together, these studies suggest that CAIX expression and activity is associated with metabolic dysfunction in MDA-MB-231 cells. ..
- Winum J, Cecchi A, Montero J, Innocenti A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with boron-containing sulfonamides, sulfamides, and sulfamates: toward agents for boron neutron capture therapy of hypoxic. Bioorg Med Chem Lett. 2005;15:3302-6 pubmed
- Di Fiore A, Pedone C, D Ambrosio K, Scozzafava A, De Simone G, Supuran C. Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II "selective" inhibitor celecoxib. Bioorg Med Chem Lett. 2006;16:437-42 pubmed..These different binding modes allow for the further drug design of various CA inhibitors belonging to the benzenesulfonamide class. ..
- Nishimori I, Minakuchi T, Morimoto K, Sano S, Onishi S, Takeuchi H, et al. Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. J Med Chem. 2006;49:2117-26 pubmed..25-3.48, showing thus some selectivity for inhibiting the bacterial enzyme. Since hpCA is essential for the survival of the pathogen in acid, it might be used as a new pharmacologic tool in the management of drug-resistant H. pylori. ..
- De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005;15:2315-20 pubmed..5 A) with residues Gln92, Val121, Phe131, Leu198, Thr200, Pro202. ..
- Innocenti A, Gulcin I, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010;20:5050-3 pubmed publisher..These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors, based on such less investigated scaffolds. ..
- Leaf D, Goldfarb D. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985). 2007;102:1313-22 pubmed
- Cianchi F, Vinci M, Supuran C, Peruzzi B, De Giuli P, Fasolis G, et al. Selective inhibition of carbonic anhydrase IX decreases cell proliferation and induces ceramide-mediated apoptosis in human cancer cells. J Pharmacol Exp Ther. 2010;334:710-9 pubmed publisher..The ability of CA inhibitors to decrease pH(i) might trigger cell apoptosis through mediation of ceramide synthesis. Activation of this apoptotic cascade probably is mediated by inhibition of the CA IX isoform. ..
- Faisy C, Mokline A, Sanchez O, Tadie J, Fagon J. Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation. Intensive Care Med. 2010;36:859-63 pubmed publisher..To evaluate the effects of a single daily dose of acetazolamide (ACET) on metabolic alkalosis and respiratory parameters in weaning chronic obstructive pulmonary disease (COPD) patients from invasive mechanical ventilation...
- Supuran C, Scozzafava A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg Med Chem. 2007;15:4336-50 pubmed
- Radhakrishnan R, Sluka K. Acetazolamide, a carbonic anhydrase inhibitor, reverses inflammation-induced thermal hyperalgesia in rats. J Pharmacol Exp Ther. 2005;313:921-7 pubmed..It is possible that the inhibition of ion channels and/or the inhibition of spinally located CAs contribute to the observed antihyperalgesia. ..
- Höhne C, Pickerodt P, Francis R, Boemke W, Swenson E. Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition. Am J Physiol Lung Cell Mol Physiol. 2007;292:L178-84 pubmed..is dependent on carbonic anhydrase inhibition by testing other potent heterocyclic sulfonamide carbonic anhydrase inhibitors. Six conscious dogs were studied in five protocols: 1) controls, 2) low-dose intravenous acetazolamide ..
- Innocenti A, Hall R, Schlicker C, Scozzafava A, Steegborn C, Muhlschlegel F, et al. Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides. Bioorg Med Chem. 2009;17:4503-9 pubmed publisher..Such compounds may be useful for the design of antifungal agents possessing a new mechanism of action. ..
- Tricarico D, Lovaglio S, Mele A, Rotondo G, Mancinelli E, Meola G, et al. Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted rats. Br J Pharmacol. 2008;154:183-90 pubmed publisher..Acetazolamide prevents vacuolar myopathy in K(+)-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA. ..