Synthesis and carbonic anhydrase I, II, IX and XII inhibition studies of 4-N,N-disubstituted sulfanilamides incorporating 4,4,4-trifluoro-3-oxo-but-1-enyl, phenacylthiourea and imidazol-2(3H)-one/thione moieties

被引:24
作者
Congiu, Cenzo [1 ]
Onnis, Valentina [1 ]
Balboni, Gianfranco [1 ]
Supuran, Claudiu T. [2 ,3 ]
机构
[1] Univ Cagliari, Dept Life & Environm Sci, I-09124 Cagliari, Italy
[2] Univ Firenze, Lab Chim Bioinorgan, I-50019 Florence, Italy
[3] Univ Firenze, Dipartimento NEIROFABA, Sez Sci Farmaceut & Nutraceut, I-50019 Florence, Italy
关键词
Carbonic anhydrase; Isoforms I; II; IX; XII; Sulfonamide; Sulfanilamide; Tumor-associated enzymes; AROMATIC/HETEROCYCLIC SULFONAMIDES; BENZENE SULFONAMIDES; CYANAMIDE HYDRATION; TRYPANOSOMA-CRUZI; POTENT INHIBITORS; ANION INHIBITION; CAUSATIVE AGENT; PATENT; ALPHA; BETA;
D O I
10.1016/j.bmcl.2014.02.030
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of sulfonamides incorporating the sulfanilamide ( SA) scaffold were prepared. Reaction of the 4-amino moiety of SA with benzyl chlorides or substituted bromoacetophenones afforded the derivatives which were then reacted with 1,1,1-trifluoro-4-isobutoxybut-3-en-2-one leading to a series of 4-N,N-disubstituted SAs. The key intermediates were also reacted with ethoxycarbonyl isothiocyanate leading to thioureas or were cyclized in the presence of potassium cyanate/isothiocyanate to the corresponding imidazol-2(3H)-one/thiones. The new compounds were tested as inhibitors of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, and the transmembrane, tumor-associated CA IX and XII. These sulfonamides were ineffective CA I and II inhibitors but were nanomolar CA IX and XII inhibitors, making them of interest as clinical candidates for antitumor/antimetastasis applications. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1776 / 1779
页数:4
相关论文
共 59 条
[21]   Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction [J].
Guerri, A ;
Briganti, F ;
Scozzafava, A ;
Supuran, CT ;
Mangani, S .
BIOCHEMISTRY, 2000, 39 (40) :12391-12397
[22]   Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors [J].
Guzel, Oezlen ;
Innocenti, Alessio ;
Scozzafava, Andrea ;
Salman, Aydin ;
Supuran, Claudiu T. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (12) :3170-3173
[23]   Carbonic anhydrase inhibitors. Aromatic/heterocyclic sulfonamides incorporating phenacetyl, pyridylacetyl and thienylacetyl tails act as potent inhibitors of human mitochondrial isoforms VA and VB [J].
Guzel, Ozlen ;
Innocenti, Alessio ;
Scozzafava, Andrea ;
Salman, Aydin ;
Supuran, Claudiu T. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (14) :4894-4899
[24]   Structural study of the location of the phenyl tail of benzene sulfonamides and the effect on human carbonic anhydrase inhibition [J].
Guzel-Akdemir, Ozlen ;
Biswas, Shyamasri ;
Lastra, Katherine ;
McKenna, Robert ;
Supuran, Claudiu T. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (21) :6674-6680
[25]   o-Benzenedisulfonimido-sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII [J].
Guzel-Akdemir, Ozlen ;
Akdemir, Atilla ;
Isik, Semra ;
Vullo, Daniela ;
Supuran, Claudiu T. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (06) :1386-1391
[26]   Paraoxon, 4-nitrophenyl phosphate and acetate are substrates of α- but not of β-, γ- and ζ-carbonic anhydrases [J].
Innocenti, Alessio ;
Supuran, Claudiu T. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (21) :6208-6212
[27]   Simple methanesulfonates are hydrolyzed by the sulfatase carbonic anhydrase activity [J].
Kazancioglu, Elif Akin ;
Guney, Murat ;
Senturk, Murat ;
Supuran, Claudiu T. .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2012, 27 (06) :880-885
[28]  
KHALIFAH RG, 1971, J BIOL CHEM, V246, P2561
[29]   Promiscuity of Carbonic Anhydrase II. Unexpected Ester Hydrolysis of Carbohydrate-Based Sulfamate Inhibitors [J].
Lopez, Marie ;
Hoan Vu ;
Wang, Conan K. ;
Wolf, Maarten G. ;
Groenhof, Gerrit ;
Innocenti, Alessio ;
Supuran, Claudiu T. ;
Poulsen, Sally-Ann .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (45) :18452-18462
[30]   Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX Inhibitors [J].
Lou, Yuanmei ;
McDonald, Paul C. ;
Oloumi, Arusha ;
Chia, Stephen ;
Ostlund, Christina ;
Ahmadi, Ardalan ;
Kyle, Alastair ;
Keller, Ulrich Auf Dem ;
Leung, Samuel ;
Huntsman, David ;
Clarke, Blaise ;
Sutherland, Brent W. ;
Waterhouse, Dawn ;
Bally, Marcel ;
Roskelley, Calvin ;
Overall, Christopher M. ;
Minchinton, Andrew ;
Pacchiano, Fabio ;
Carta, Fabrizio ;
Scozzafava, Andrea ;
Touisni, Nadia ;
Winum, Jean-Yves ;
Supuran, Claudiu T. ;
Dedhar, Shoukat .
CANCER RESEARCH, 2011, 71 (09) :3364-3376