Carbonic anhydrase inhibitors: Cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides

被引:101
作者
Nishimori, Isao [2 ]
Minakuchi, Tomoko [2 ]
Onishi, Saburo [2 ]
Vullo, Daniela [1 ]
Cecchi, Alessandro [1 ]
Scozzafava, Andrea [1 ]
Supuran, Claudiu T. [1 ]
机构
[1] Univ Florence, Lab Chim Bioinorgan, I-50019 Florence, Italy
[2] Kochi Med Sch, Dept Gastroenterol & Hepatol, Kochi 7838505, Japan
关键词
carbonic anhydrase; isozyme I; II; III; sulfonamide; sulfamate; prontosil;
D O I
10.1016/j.bmc.2007.08.037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isozyme III (hCA III) has been cloned and purified by the GST-fusion protein method. Recombinant pure hCA III had the following kinetic parameters for the CO2 hydration reaction at 20 degrees C and pH 7.5: k(cat) of 1.3 x 10(4) s(-1) and k(cat)/ K-M of 2.5 x 10(5) M-1 s(-1), being a slower catalyst for the physiological reaction as compared to the genetically related cytosolic isoforms hCA I and II. An inhibition study with a library of sulfonamides and one sulfamate, some which are clinically used compounds, is reported. hCA III is less prone to be inhibited by these compounds as compared to hCA I and II for which many low nanomolar inhibitors were detected earlier. The best hCA III inhibitors were prontosil, sulpiride, indisulam, benzolamide, aminobenzolamide, and 4-amino-6-chloro-benzene-1,3-disulfonamide which showed K(I)s in the range of 2.3-18.1 mu M. Clinically used compounds such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, brinzolamide, topiramate, zonisamide, celecoxib, and valdecoxib were less effective hCA III inhibitors, with affinities in the range of 154-2200 mu M. This is the first study in which low micromolar hCA III inhibitors are reported. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7229 / 7236
页数:8
相关论文
共 46 条
[1]   Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride [J].
Abbate, F ;
Coetzee, A ;
Casini, A ;
Ciattini, S ;
Scozzafava, A ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (02) :337-341
[2]   Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX [J].
Abbate, F ;
Casini, A ;
Owa, T ;
Scozzafava, A ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (01) :217-223
[3]   Effects of leptin and insulin on CA III expression in rat adipose tissue [J].
Alver, A ;
Uçar, F ;
Keha, EE ;
Kalay, E ;
Ovali, E .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2004, 19 (03) :279-281
[4]   The effect of carbonic anhydrase inhibition on leptin secretion by rat adipose tissue [J].
Alver, A ;
Keha, EE ;
Uçar, F ;
Ovali, E .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2004, 19 (02) :181-184
[5]   Structural analysis of inhibitor binding to human carbonic anhydrase II [J].
Boriack-Sjodin, PA ;
Zeitlin, S ;
Chen, HH ;
Crenshaw, L ;
Gross, S ;
Dantanarayana, A ;
Delgado, P ;
May, JA ;
Dean, T ;
Christianson, DW .
PROTEIN SCIENCE, 1998, 7 (12) :2483-2489
[6]  
CARTER N, 1978, Biochemical Society Transactions, V6, P552
[7]   Carbonic anhydrase inhibitors:: SAR and x-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with Isozymes I, II and IV [J].
Casini, A ;
Antel, J ;
Abbate, F ;
Scozzafava, A ;
David, S ;
Waldeck, H ;
Schäfer, S ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (05) :841-845
[8]  
Chegwidden W. Richard, 1991, P101
[9]   Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies [J].
De Simone, G ;
Di Fiore, A ;
Menchise, V ;
Pedone, C ;
Antel, J ;
Casini, A ;
Scozzafava, A ;
Wurl, M ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (09) :2315-2320
[10]   Antiobesity carbonic anhydrase inhibitors [J].
De Simone, Giuseppina ;
Supuran, Claudiu T. .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2007, 7 (09) :879-884