Carbonic anhydrase inhibitors. Phenols incorporating 2-or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase

被引：51

作者：

Bilginer, Sinan ^{[1
]}

Unluer, Elif ^{[1
]}

Gul, Halise Inci ^{[1
]}

Mete, Ebru ^{[2
]}

Isik, Semra ^{[3
]}

Vullo, Daniela ^{[3
]}

Ozensoy-Guler, Ozen ^{[3
,4
]}

Beyaztas, Serap ^{[3
]}

Capasso, Clemente ^{[5
]}

Supuran, Claudiu T. ^{[3
,6
]}

机构：

[1] Ataturk Univ, Fac Pharm, Dept Pharmaceut Chem, Erzurum, Turkey

[2] Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkey

[3] Univ Florence, Lab Chim Bioinorgan, Florence, Italy

[4] Yildirim Beyazit Univ, Fac Med, Dept Med Biol, Ankara, Turkey

[5] CNR, Ist Biochim Proteine, I-80131 Naples, Italy

[6] Univ Florence, Sez Sci Farmaceut Nutraceut, Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2014年 / 29卷 / 04期

关键词：

Antifungalscarbonic anhydrase; phenols; pyridylethenyl-carbonyl; Saccharomyces cerevisiae; CLASS ENZYME; CANDIDA-GLABRATA; BENZENESULFONAMIDES; SULFONAMIDES;

D O I：

10.3109/14756366.2013.806497

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of phenols incorporating tertiary amine and trans-pyridylethenyl-carbonyl moieties were assayed as inhibitors of the beta-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. One of these compounds was a low nanomolar ScCA inhibitor, whereas the remaining ones inhibited the enzyme with K(I)s in the range of 23.5-95.4 nM. The off-target human (h) isoforms hCA I and hCA II were much less inhibited by these phenols, with K(I)s in the range of 0.78-23.5 mu M (hCA I) and 10.8-52.4 mu M (hCA II). The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged.

引用

页码：495 / 499

页数：5

共 34 条

[1]

Carbonic anhydrase inhibitors. Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase [J].

Alafeefy, Ahmed M. ;

Isik, Semra ;

Al-Jaber, Nabila A. ;

Vullo, Daniela ;

Abdel-Aziz, Hatem A. ;

Ashour, Abdelkader E. ;

Awaad, Amani S. ;

Capasso, Clemente ;

Supuran, Claudiu T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (12) :3570-3575

[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]

Bilginer S, 2013, J ENZYM INHIB MED CH, V28, P1

[4]

Acetaldehyde-derived modifications on cytosolic human carbonic anhydrases [J].

Bootorabi, Fatemeh ;

Janis, Janne ;

Hytonen, Vesa P. ;

Valjakka, Jarkko ;

Kuuslahti, Marianne ;

Vullo, Daniela ;

Niemela, Onni ;

Supuran, Claudiu T. ;

Parkkila, Seppo .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2011, 26 (06) :862-870

[5]

Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives [J].

Carta, Fabrizio ;

Innocenti, Alessio ;

Hall, Rebecca A. ;

Muehlschlegel, Fritz A. ;

Scozzafava, Andrea ;

Supuran, Claudiu T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (08) :2521-2526

[6]

Carbonic anhydrase regulation and CO2 sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog [J].

Cottier, Fabien ;

Leewattanapasuk, Worraanong ;

Kemp, Laura R. ;

Murphy, Mariana ;

Supuran, Claudiu T. ;

Kurzai, Oliver ;

Muehlschlegel, Fritz A. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (06) :1549-1554

[7]

(In)organic anions as carbonic anhydrase inhibitors [J].

De Simone, Giuseppina ;

Supuran, Claudiu T. .

JOURNAL OF INORGANIC BIOCHEMISTRY, 2012, 111 :117-129

[8]

Carbonic anhydrase inhibitors: inhibition of human and bovine isoenzymes by benzenesulphonamides, cyclitols and phenolic compounds [J].

Ekinci, Deniz ;

Kurbanoglu, Namudar I. ;

Salamci, Emine ;

Senturk, Murat ;

Supuran, Claudiu T. .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2012, 27 (06) :845-848

[9]

Carbonic anhydrases in fungi [J].

Elleuche, Skander ;

Poeggeler, Stefanie .

MICROBIOLOGY-SGM, 2010, 156 :23-29

[10]

HALL RA, 2009, DRUG DESIGN ZINC ENZ, P301

← 1 2 3 4 →