N-Hydroxyurea -: A versatile zinc binding function in the design of metalloenzyme inhibitors

被引：32

作者：

Temperini, Claudia ^{[1
]}

Innocenti, Alessio ^{[1
]}

Scozzafava, Andrea ^{[1
]}

Supuran, Claudiu T. ^{[1
]}

机构：

[1] Univ Florence, Lab Chim Bioinorgan, I-50019 Sesto Fiorentino, Firenze, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 16期

关键词：

zinc enzyme; carbonic anhydrase; MMP; N-hydroxyurea; X-ray crystallography; enzyme-inhibitor;

D O I：

10.1016/j.bmcl.2006.05.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-Hydroxyurea binds both to carbonic anhydrase (CA) and to matrix metalloproteinases (MMPs). X-ray crystallography showed N-hydroxyurea to bind in a bidentate mode by means of the oxygen and nitrogen atoms of the NHOH moiety to the Zn(II) ion of CA, participating in a network of hydrogen bonds with a water molecule and Thr199. A derivatized N-hydroxyurea showed low-micromolar affinity for several CAs. This simple zinc binding function may be exploited for obtaining potent metalloenzyme inhibitors, due to its versatility of binding to the metal ion present in the active site of such enzymes. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：4316 / 4320

页数：5

共 31 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] Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase [J].

Abbate, F ;

Winum, JY ;

Potter, BVL ;

Casini, A ;

Montero, JL ;

Scozzafava, A ;

Supuran, CT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (01) :231-234

[4] Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a topically acting antiglaucoma sulfonamide [J].

Abbate, F ;

Casini, A ;

Scozzafava, A ;

Supuran, CT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (09) :2357-2361

[5] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[6]

Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254

[7] N-hydroxyurea as zinc binding group in matrix metalloproteinase inhibition:: Mode of binding in a complex with MMP-8 [J].

Campestre, C ;

Agamennone, M ;

Tortorella, P ;

Preziuso, S ;

Biasone, A ;

Gavuzzo, E ;

Pochetti, G ;

Mazza, F ;

Hiller, O ;

Tschesche, H ;

Consalvi, V ;

Gallina, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (01) :20-24

[8] 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

[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] Carbonic anhydrase inhibitors: X-ray crystal structure of a benzenesulfonamide strong CA II and CA IX inhibitor bearing a pentafluorophenylaminothioureido tail in complex with isozyme II [J].

Di Fiore, A ;

De Simone, G ;

Menchise, V ;

Pedone, C ;

Casini, A ;

Scozzafava, A ;

Supuran, CT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (07) :1937-1942

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