Inhibition of tumor-associated human carbonic anhydrase isozymes IX and XII by a new class of substituted-phenylacetamido aromatic sulfonamides

被引：21

作者：

Akdemir, Atilla ^{[1
]}

Guzel-Akdemir, Ozlen ^{[2
]}

Scozzafava, Andrea ^{[3
]}

Capasso, Clemente ^{[4
]}

Supuran, Claudiu T. ^{[3
,5
]}

机构：

[1] Bezmialem Vakif Univ, Fac Pharm, Dept Pharmacol, TR-34093 Istanbul, Turkey

[2] Istanbul Univ, Fac Pharm, Dept Pharmaceut Chem, TR-34116 Istanbul, Turkey

[3] Univ Florence, Lab Chim Bioinorgan, I-50019 Florence, Italy

[4] CNR, Ist Biochim Prot, I-80131 Naples, Italy

[5] Univ Florence, NEUROFARBA Dept, Sez Sci Farmaceut, I-50019 Florence, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 17期

关键词：

Carbonic anhydrases; Cytosolic isoforms I and II; Tumor-associated isoforms IX and XII; Sulfonamides; Docking; X-RAY; CRYSTAL-STRUCTURE; ACTIVE-SITE; ISOFORMS; DIOXIDE; DOMAIN;

D O I：

10.1016/j.bmc.2013.06.029

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：

Here, we investigate 28 structurally new sulfonamides and their subsequent testing for enzyme inhibition of cytosolic and tumor-associated carbonic anhydrases (CAs, EC 4.2.1.1). The compounds showed very potent inhibition of four physiologically relevant human (h) CA isoforms, namely hCA I, II, IX and XII. Interestingly, the K-I values were in the nanomolar range for the tumor-associated hCA IX and hCA XII. Docking studies have revealed details regarding the very favorable interactions between the scaffolds of this new class of inhibitors and the active sites of the investigated CA isoforms. As there are reported cases of tumors overexpressing both CA II and IX, such potent inhibitors for the two isoforms as those detected in this work, may have applications for targeting more than one CA present in tumors. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5228 / 5232

页数：5

共 31 条

[1] Update on carbonic anhydrase inhibitors: a patent review (2008-2011) [J].

Aggarwal, Mayank ;

McKenna, Robert .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2012, 22 (08) :903-915

[2] Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms? [J].

Alterio, Vincenzo ;

Di Fiore, Anna ;

D'Ambrosio, Katia ;

Supuran, Claudiu T. ;

De Simone, Giuseppina .

CHEMICAL REVIEWS, 2012, 112 (08) :4421-4468

[3] The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex [J].

Alterio, Vincenzo ;

Monti, Simona Maria ;

Truppo, Emanuela ;

Pedone, Carlo ;

Supuran, Claudiu T. ;

De Simone, Giuseppina .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2010, 8 (15) :3528-3533

[4] Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX [J].

Alterio, Vincenzo ;

Hilvo, Mika ;

Di Fiore, Anna ;

Supuran, Claudiu T. ;

Pan, Peiwen ;

Parkkila, Seppo ;

Scaloni, Andrea ;

Pastorek, Jaromir ;

Pastorekova, Silvia ;

Pedone, Carlo ;

Scozzafava, Andrea ;

Monti, Simona Maria ;

De Simone, Giuseppina .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (38) :16233-16238

[5] Carbonic anhydrase inhibitors: X-ray and molecular modeling study for the interaction of a fluorescent antitumor sulfonamide with isozyme II and IX [J].

Alterio, Vincenzo ;

Vitale, Rosa Maria ;

Monti, Simona Maria ;

Pedone, Carlo ;

Scozzafava, Andrea ;

Cecchi, Alessandro ;

De Simone, Giuseppina ;

Supuran, Claudiu T. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (25) :8329-8335

[6] Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors [J].

Avvaru, Balendu Sankara ;

Wagner, Jason M. ;

Maresca, Alfonso ;

Scozzafava, Andrea ;

Robbins, Arthur H. ;

Supuran, Claudiu T. ;

McKenna, Robert .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (15) :4376-4381

[7] A Short, Strong Hydrogen Bond in the Active Site of Human Carbonic Anhydrase II [J].

Avvaru, Balendu Sankara ;

Kim, Chae Un ;

Sippel, Katherine H. ;

Gruner, Sol M. ;

Agbandje-McKenna, Mavis ;

Silverman, David N. ;

McKenna, Robert .

BIOCHEMISTRY, 2010, 49 (02) :249-251

[8] Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]-thiadiazole-7-sulphonamides [J].

Baranauskiene, Lina ;

Hilvo, Mika ;

Matuliene, Jurgita ;

Golovenko, Dmitrij ;

Manakova, Elena ;

Dudutiene, Virginija ;

Michailoviene, Vilma ;

Torresan, Jolanta ;

Jachno, Jelena ;

Parkkila, Seppo ;

Maresca, Alfonso ;

Supuran, Claudiu T. ;

Grazulis, Saulius ;

Matulis, Daumantas .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2010, 25 (06) :863-870

[9] Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: Solution and X-ray crystallographic studies [J].

Carta, Fabrizio ;

Garaj, Vladimir ;

Maresca, Alfonso ;

Wagner, Jason ;

Avvaru, Balendu Sankara ;

Robbins, Arthur H. ;

Scozzafava, Andrea ;

McKenna, Robert ;

Supuran, Claudiu T. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (10) :3105-3119

[10] 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

← 1 2 3 4 →