Carbonic anhydrase inhibitors:: SAR and x-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with Isozymes I, II and IV

被引：219
作者：
Casini, A
Antel, J
Abbate, F
Scozzafava, A
David, S
Waldeck, H
Schäfer, S
Supuran, CT
机构：
[1] Solvay Pharmaceut GMBH, D-30173 Hannover, Germany
[2] Univ Florence, Dipartimento Chim, I-50019 Sesto Fiorentino, Firenze, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 05期
关键词：
D O I：
10.1016/S0960-894X(03)00029-5
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of sugar sulfamate/sulfamide derivatives were prepared and assayed as inhibitors of three carbonic anhydrase (CA) isozymes, hCA 1, hCA 11 and bCA IV. Best inhibitory properties were observed for the clinically used antiepileptic drug topiramate, which is a low nanomolar CA 11 inhibitor, and possesses good inhibitory properties against the other two isozymes investigated here, similarly with acetazolamide, methazolamide or dichlorophenamide. The X-ray structure of the complex of topiramate with hCA 11 has been solved and it revealed a very tight association of the inhibitor, with a network of seven strong hydrogen bonds fixing topiramate within the active site, in addition to the Zn(II) coordination through the ionized sulfamate moiety. Structural changes in this series of sugar derivatives led to compounds with diminished CA inhibitory properties as compared to topiramate. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：841 / 845
页数：5
相关论文
共 23 条
[1]   Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: Role of hydrogen-bonding networks in ligand binding and drug design [J].
Abbate, F ;
Supuran, CT ;
Scozzafava, A ;
Orioli, P ;
Stubbs, MT ;
Klebe, G .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (17) :3583-3587
[2]  
Bourgeois Blaise F. D., 2000, Journal of Child Neurology, V15, pS27
[3]   Catalysis by metal-activated hydroxide in zinc and manganese metalloenzymes [J].
Christianson, DW ;
Cox, JD .
ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :33-57
[4]   Topiramate as an inhibitor of carbonic anhydrase isoenzymes [J].
Dodgson, SJ ;
Shank, RP ;
Maryanoff, BE .
EPILEPSIA, 2000, 41 :S35-S39
[5]   Anticonvulsant activity of topiramate and phenytoin in a rat model of ischemia-induced epilepsy [J].
Edmonds, HL ;
Jiang, YD ;
Zhang, PY ;
Shank, RP .
LIFE SCIENCES, 1996, 59 (10) :PL127-PL131
[6]   IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS [J].
JONES, TA ;
ZOU, JY ;
COWAN, SW ;
KJELDGAARD, M .
ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 :110-119
[7]   INHIBITION AND CATALYSIS OF CARBONIC-ANHYDRASE - RECENT CRYSTALLOGRAPHIC ANALYSES [J].
LILJAS, A ;
HAKANSSON, K ;
JONSSON, BH ;
XUE, YF .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 219 (1-2) :1-10
[8]  
LINDSKOG S, 1983, COORDINATION CHEM ME, P49
[9]   Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives [J].
Maryanoff, BE ;
Costanzo, MJ ;
Nortey, SO ;
Greco, MN ;
Shank, RP ;
Schupsky, JJ ;
Ortegon, MP ;
Vaught, JL .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (08) :1315-1343
[10]   Carbonic anhydrase inhibitors: Anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties [J].
Masereel, B ;
Rolin, S ;
Abbate, F ;
Scozzafava, A ;
Supuran, CT .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (02) :312-320
123