References

Akisawa, Y., Nishimori, I., Taniuchi, K., Okamoto, N., Takeuchi, T., Sonobe, H. et al. (2003) Expression of carbonic anhydrase-related protein CA-RP VIII in non-small lung cancer. Virchows Archives, 442, 66-70. Barnea, G., Grumet, M., Milev, P., Silvennoinen, O., Levy, J.B., Sap, J., and Schlessinger, J. (1994) Receptor tyrosine phosphatase beta is expressed in the form of proteoglycan and binds to the extracellular matrix protein tenascin. Journal of Biological Chemistry 269, 14349-14352....

Connections Of Caas With Physiopathology Possible Clinical Developments

Many naturally occurring compounds found in the human body activate CAs at physiological concentrations (Supuran et al. 1991 Supuran and Balaban 1994 Scoz-zafava and Supuran 2002b). Examples are histamine, serotonin, dopamine, adrenaline, noradrenaline and other catecholamines, which are important autacoids some amino acids and oligopeptides, some of which are hormones (Supuran and Puscas 1994) and others (such as b-alanyl-histidine) have been proved to possess different physiological roles...

Sulfonamides In The Treatment Of Glaucoma

Glaucoma is a chronic, degenerative eye disease, characterized by high IOP, which causes irreversible damage to the optic nerve head, and, as a result, the progressive loss of visual function and eventually blindness (Bartlett and Jaanus 1989 Maren 1992, 1995). Elevated IOP (ocular hypertension) is generally indicative of an early stage of the disease (Bartlett and Jaanus 1989 Soltau and Zimmerman 2002 Hoyng and Kitazawa 2002). CAIs represent the most physiological treatment of glaucoma,...

Ca Inhibition As An Approach To Anticancer Therapy

Although there are no complete data that would link the phenotypic or therapeutic effects of CA inhibition as a means of tumor pH manipulation to perturbed activity of particular CA isozymes, the literature available so far clearly indicates that this is an exploitable avenue toward treating cancer. Teicher and co-workers (1993) showed that acetalozamide, a prototype carbonic anhydrase inhibitor (CAI) of several CA isozymes, reduced in vivo growth of tumors when given alone and produced...

CAIs In The Kidney

A number of studies that use CAIs have provided the functional basis on the role of CA activity in renal acidification. Despite their promising past, CAIs have not been very useful in the therapy of renal diseases (Supuran and Scozzafava 2000). Acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide can be used to treat edema induced by drugs or congestive heart failure (Supuran and Scozzafava 2000). These inhibitors can, however, cause several undesired side effects, such as...

CAIs In Macular Edema Macular Degeneration And Related Ocular Pathologies

Optic nerve blood flow is diminished in the eyes of primary open-angle glaucoma suspects and patients (Pilts-Seymour et al. 2001). Because sulfonamides with CAI properties act as vasodilators (Supuran and Scozzafava 2000), this might explain the use of such drugs for treating retinal edema and age-related macular degeneration. In consequence, these pharmacological agents represent a new approach for improving visual function. Retinal edema (also referred to as cystoid macular edema) consists of...

Catalytic And Inhibition Mechanisms Of Cas 121 aCAs

The Zn II ion of CAs is essential for catalysis Lindskog and Silverman 2000 Christianson and Fierke 1996 Bertini et al. 1982 Supuran et al. 2003 . X-ray Ar 2,4-dinitrophenyl PhCH2OCOCl H2O PhCH2OH CO2 HCl 1.8 Ar 2,4-dinitrophenyl PhCH2OCOCl H2O PhCH2OH CO2 HCl 1.8 RSO2Cl H2O RSO3H HCl 1.9 FIGURE 1.1 Reactions catalyzed by a-CAs. Reproduced from Supuran, C.T. et al. 2003 Medicinal Research Reviews 23, 146-189, John Wiley amp Sons. With permission. crystallographic data show that the metal ion is...

Antitumor Sulfonamides

There are many connections between CA and cancer for example, some CA isozymes CA IX and XII are predominantly found in cancer cells and not in the normal counterparts Pastorek et al. 1994 Pastorekova et al. 1997 Chegwidden et al. 2001 . Teicher et al. 1993 reported that acetazolamide 4.44 functions as a modulator in anticancer therapies in combination with different cytotoxic agents, such as alkylating agents, nucleoside analogs or platinum derivatives. It was hypothesized that the anticancer...

Introduction

The discovery of CA inhibition with sulfanilamide 4.1 by Mann and Keilin 1940 was the beginning of a great adventure that led to important drugs widely used to treat or prevent a multitude of diseases. Sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing, among others, antibacterial, antitumor, anticarbonic anhydrase CA , diuretic, hypoglycemic, anti-thyroid or protease inhibitory activity Northey 1948 Maren 1967 Scozzafava et al. 2003...

Physiological Functions Of Cas

It is not clear whether the other reactions catalyzed by CAs Figure 1.1 except for CO2 hydration bicarbonate dehydration have physiological relevance Supuran et al. 2003 . Thus, at present, only the reaction in Equation 1.1, Figure 1.1, is considered to be the physiological one in which these enzymes are involved. In prokaryotes, CAs possess two general functions 1 transport of CO2 bicar-bonate between different tissues of the organism and 2 provide CO2 bicarbonate for enzymatic reactions Smith...