References Pbg
Abbate, F., Casini, A., Owa, T., Scozzafava, A., Supuran, C.T. 2004 Carbonic anhydrase inhibitors E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isoenzymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorganic and Medicinal Chemistry Letters 14, 217-223. Ashida, S., Nishimori, I., Tanimura, M., Onishi, S., and Shuin, T. 2002 Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell...
References Fix
Arcas, J., Ferrer, T., Roche, M., Bermejo-Martinez, A., and Lopez-Martin, V. 2001 Hypo-hidrosis related to the administration of topiramate to children. Epilepsia 42, 1363-1365. Briggman, J.V., Tashian, R.E., and Spicer, S.S. 1983 Immunohistochemical localization of carbonic anhydrase I and II in eccrine sweat glands from control subjects and patients with cystic fibrosis. American Journal of Pathology 112, 250-257. Burtscher, M., and Likar, R. 2002 Leukonichia following high altitude exposure...
Applications Of Metal Complexes Of Sulfonamides In Therapy
The CA inhibitory properties of numerous metal sulfonamide complexes mentioned here have been investigated in detail, mostly against the red cell isozymes hCA I and hCA II, but in some cases also against the membrane-bound isozyme bCA IV h human, b bovine isozyme reviewed in Alzuet et al. 1994c and Supuran 1994 . Such studies surprisingly indicated that the metal complexes are 10 to 100 times more potent inhibitors of these isozymes as compared to the corresponding parent sulfonamides, making...
Acknowledgements
We are indebted to Elsevier for providing permission to reproduce Table 12 from Clare, B.W., and Supuran, C.T. 1007 European Journal of Medicinal Chemistry 32, 311-319 Table 5 from Supuran, C.T., and Clare, B.W. 1998 European Journal of Medicinal Chemistry 33, 489-500 and Table 6 from Supuran, C.T., and Clare, B.W. European Journal of Medicinal Chemistry 34, 463-474. We also thank the publishing house of the Romanian Academy for providing permission to publish Tables 7 and 10 from the review...
References Ayd
Abbate, F., Supuran, C.T., Scozzafava, A., Orioli, P., Stubbs, M., and Klebe, G. 2002 Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhy-drase inhibitors Role of hydrogen-bonding networks in ligand binding and drug design. Journal of Medicinal Chemistry 45, 3583-3587. Antonaroli, S., Bianco, A., Brufani, M., Cellai, L., Lo Baido, G., Potier, E., Bonomi, L., Perfetti, S., Fiaschi, A.I., and Segre, G. 1992 Acetazolamide-like carbonic anhydrase inhibitors with topical...
Introduction Kdw
The inhibition of carbonic anhydrase CA was investigated almost immediately after its discovery Meldrum and Roughton 1933 Forster 2000 , and was decisive in understanding its functioning Maren and Sanyal 1983 . Since then, many carbonic anhydrase inhibitors CAIs have been discovered or invented the field has been periodically reviewed Bertini et al. 1982 Coleman 1975 Dodgson et al. 1991 Mansoor et al. 2000 Maren 1967, 2000 Maren and Sanyal 1983 Pocker and Sarkanen 1978 Silverman and Lindskog...
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...
So2nh2 1
for both CA II and CA IV, and, more importantly, were unable to cross the plasma membranes in vivo Supuran et al. 2000b Scozzafava et al. 2000c . In two model systems human red cells and perfusion experiments in rats , this new class of potent, positively charged CAIs was able to discriminate the membrane-bound from the cytosolic isozymes, selectively inhibiting CA IV only Supuran et al. 2000b Scozzafava et al. 2000c . Such data are important both for specific in vivo inhibition of...
References Erk
Abbate, F., Supuran, C.T., Scozzafava, A., Orioli, P., Stubbs, M.T. and Klebe, G. 2002 Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhy-drase inhibitors Role of hydrogen-bonding networks in ligand binding and drug design. Journal of Medicinal Chemistry 45, 3583-3587. Antel, J. 1999 Integration of combinatorial chemistry and structure-based drug design. Current Opinion in Drug Discovery and Development 2, 224-233. Aribi, A.M., and Stringer, J.L. 2002 Effects of...
Info Xjq
Source From Roblin, R.O., Jr., and Clapp, J.W. 1950 Journal of the American Chemical Society 72, 4890-4892 and Supuran, C.T. 1994 In Carbonic Anhydrase and Modulation of Physiologic and Pathologic Processes in the Organism, Puscas, I., Ed., Helicon Press, Timisoara, Romania, pp. 29-111. With permission. Source From Roblin, R.O., Jr., and Clapp, J.W. 1950 Journal of the American Chemical Society 72, 4890-4892 and Supuran, C.T. 1994 In Carbonic Anhydrase and Modulation of Physiologic and...
Info Vzr
Source From Vaughan, J.R. et al. 1956 Journal of Organic Chemistry 21, 700-771 and Supuran, C.T. 1994 In Carbonic Anhydrase and Modulation of Physiologic and Pathologic Processes in the Organism, Puscas, I., Ed., Helicon Press, Timisoara, Romania, pp. 29-111. With permission. Source From Vaughan, J.R. et al. 1956 Journal of Organic Chemistry 21, 700-771 and Supuran, C.T. 1994 In Carbonic Anhydrase and Modulation of Physiologic and Pathologic Processes in the Organism, Puscas, I., Ed., Helicon...
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...
References
Abbate, F., Casini, A., Scozzafava, A., and Supuran, C.T., 2003 Carbonic anhydrase inhibitors x-ray crystallographic structure of the adduct of human isozyme II with the perfluorobenzoyl analogue of methazolamide Implications for the drug design of fluorinated inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 18, 303-308. Abbate, F., Supuran, C.T., Scozzafava, A., Orioli, P., Stubbs, M.T., and Klebe, G. 2002 Nonaromatic sulfonamide group as an ideal anchor for the design of...
Introduction Gam
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...
So2nh2
configuration , the alkylation product with the desired stereochemistry, 4.147, was obtained. Cyclization of 4.147 after hydrolysis of the ester moiety was achieved in the presence of trifluoroacetic anhydride in toluene, when ketone 4.148 was obtained in good yields. Its reduction with LiAlH4 in 95 yield gave the cis-alcohol 4.149a, which was epimerized to 4.149b in the presence of cold 1 N H2SO4. A mixture of 76 24 trans cis epimeric alcohols resulted, which was oxidized with H2O2 Na2WO4 to...
References Glm
Altomare, C., Tsai, R.-S., el Tayar, N., Testa, B., Carotti, A., Cellamare, S., and DeBenedetti, P.G. 1991a Determination of lipophilicity and hydrogen bond donor acidity of bioactive sulfonyl-containing compounds by reversed phase HPLC and centrifugal partition chromatography and their application to structure-activity relationships. Journal of Pharmacy and Pharmacology 43, 191-197. Altomare, C., Tsai, R.-S., El Tayar, N., Testa, B., Carrupt, P.-A., Carotti, A., and DeBenedetti, P.G. 1991b...