Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: Synthesis, biological evaluation and molecular modelling studies

被引：36

作者：

D'Ascenzio, Melissa ^{[1
]}

Carradori, Simone ^{[1
]}

Secci, Daniela ^{[1
]}

Vullo, Daniela ^{[2
]}

Ceruso, Mariangela ^{[2
]}

Akdemir, Atilla ^{[4
]}

Supuran, Claudiu T. ^{[2
,3
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, I-00185 Rome, Italy

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

[3] Univ Florence, Neurofarba Dept, Sect Pharmaceut & Nutriceut Sci, I-50019 Florence, Italy

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 15期

关键词：

Probenecid; Selective carbonic anhydrase IX inhibitors; Selective carbonic anhydrase XII inhibitors; Tertiary sulfonamides; HCA IX INHIBITORS; BREAST-CANCER; THERAPEUTIC APPLICATIONS; TERTIARY BENZENESULFONAMIDES; SULFONAMIDES; HYPOXIA; XII; METABOLISM; ADAPTATIONS; METASTASIS;

D O I：

10.1016/j.bmc.2014.06.003

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：

Novel amide derivatives of probenecid, a well-known uricosuric agent, were synthesized and evaluated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). The transmembrane isoforms (hCA IX and XII) were potently and selectively inhibited by some of them. The proposed chemical modification led to a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and enhanced the inhibitory activity against the tumour-associated hCA XII (compound 4 showed a K-i value of 15.3 nM). The enzyme inhibitory data have also been validated by docking studies of the compounds within the active site of hCA XII. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3982 / 3988

页数：7

共 45 条

[11] Oncogenic alterations of metabolism [J].

Dang, CV ;

Semenza, GL .

TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (02) :68-72

[12] Purification and characterization of carbonic anhydrase from sheep kidney and effects of sulfonamides on enzyme activity [J].

Demirdag, Ramazan ;

Comakli, Veysel ;

Senturk, Murat ;

Ekinci, Deniz ;

Kufrevioglu, O. Irfan ;

Supuran, Claudiu T. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (06) :1522-1525

[13] Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies [J].

Ebbesen, Peter ;

Pettersen, Erik O. ;

Gorr, Thomas A. ;

Jobst, Gerhard ;

Williams, Kaye ;

Kieninger, Jochen ;

Wenger, Roland H. ;

Pastorekova, Silvia ;

Dubois, Ludwig ;

Lambin, Philippe ;

Wouters, Brad G. ;

Van Den Beucken, Twan ;

Supuran, Claudiu T. ;

Poellinger, Lorenz ;

Ratcliffe, Peter ;

Kanopka, Arvydas ;

Goerlach, Agnes ;

Gasmann, Max ;

Harris, Adrian L. ;

Maxwell, Patrick ;

Scozzafava, Andrea .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2009, 24 :1-39

[14] Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer [J].

Gatenby, R. A. ;

Smallbone, K. ;

Maini, P. K. ;

Rose, F. ;

Averill, J. ;

Nagle, R. B. ;

Worrall, L. ;

Gillies, R. J. .

BRITISH JOURNAL OF CANCER, 2007, 97 (05) :646-653

[15] Why do cancers have high aerobic glycolysis? [J].

Gatenby, RA ;

Gillies, RJ .

NATURE REVIEWS CANCER, 2004, 4 (11) :891-899

[16] Carbonic anhydrase IX as a target for metastatic disease [J].

Gieling, Roben G. ;

Williams, Kaye J. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (06) :1470-1476

[17] Recent advances in research on the most novel carbonic anhydrases, CA XIII and XV [J].

Hilvo, M. ;

Innocenti, A. ;

Monti, S. M. ;

De Simone, G. ;

Supuran, C. T. ;

Parkkila, S. .

CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (07) :672-678

[18] Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche [J].

Lock, F. E. ;

McDonald, P. C. ;

Lou, Y. ;

Serrano, I. ;

Chafe, S. C. ;

Ostlund, C. ;

Aparicio, S. ;

Winum, J-Y ;

Supuran, C. T. ;

Dedhar, S. .

ONCOGENE, 2013, 32 (44) :5210-5219

[19] 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

[20] Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas [J].

Lounnas, Nadia ;

Rosilio, Celia ;

Nebout, Marielle ;

Mary, Didier ;

Griessinger, Emmanuel ;

Neffati, Zouhour ;

Chiche, Johanna ;

Spits, Hergen ;

Hagenbeek, Thijs J. ;

Asnafi, Vahid ;

Poulsen, Sally-Ann ;

Supuran, Claudiu T. ;

Peyron, Jean-Francois ;

Imbert, Veronique .

CANCER LETTERS, 2013, 333 (01) :76-88

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