3H-1,2-benzoxathiepine 2,2-dioxides: a new class of isoform-selective carbonic anhydrase inhibitors

被引：39

作者：

Pustenko, Aleksandrs ^{[1
,2
]}

Stepanovs, Dmitrijs ^{[1
]}

Zalubovskis, Raivis ^{[1
]}

Vullo, Daniela ^{[3
]}

Kazaks, Andris ^{[4
]}

Leitans, Janis ^{[4
]}

Tars, Kaspars ^{[5
]}

Supuran, Claudiu T. ^{[6
]}

机构：

[1] Latvian Inst Organ Synth, Riga, Latvia

[2] Riga Tech Univ, Fac Mat Sci & Appl Chem, Inst Technol Organ Chem, Riga, Latvia

[3] Univ Firenze, Lab Chim Bioinorgan, Dipartimento Chim, Polo Sci, Florence, Italy

[4] Latvian Biomed Res & Study Ctr, Riga, Latvia

[5] Univ Latvia, Dept Mol Biol, Fac Biol, Riga, Latvia

[6] Univ Firenze, Sez Sci Farmaceut & Nutraceut, Dipartimento Neurofarba, Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2017年 / 32卷 / 01期

关键词：

Carbonic anhydrase; sulfocoumarin; homo-sulfocoumarins; inhibitor; DRUG DISCOVERY; XII INHIBITORS; IX INHIBITORS; POTENT; SULFOCOUMARINS; COUMARINS; SULFONAMIDES; MECHANISM;

D O I：

10.1080/14756366.2017.1316720

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：

A new chemotype with carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action has been discovered, the homo-sulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) which have been designed considering the (sulfo) coumarins as lead molecules. An original synthetic strategy of a panel of such derivatives led to compounds with a unique inhibitory profile and very high selectivity for the inhibition of the tumour associated (CA IX/XII) over the cytosolic (CA I/II) isoforms. Although the CA inhibition mechanism with these new compounds is unknown for the moment, we hypothesize that it may be similar to that of the sulfocoumarins, i.e. hydrolysis to the corresponding sulfonic acids which thereafter anchor to the zinc-coordinated water molecule within the enzyme active site.

引用

页码：767 / 775

页数：9

共 59 条

[41] Targeting tumour hypoxia to prevent cancer metastasis. From biology, biosensing and technology to drug development: the METOXIA consortium [J].

Pettersen, Erik O. ;

Ebbesen, Peter ;

Gieling, Roben G. ;

Williams, Kaye J. ;

Dubois, Ludwig ;

Lambin, Philippe ;

Ward, Carol ;

Meehan, James ;

Kunkler, Ian H. ;

Langdon, Simon P. ;

Ree, Anne H. ;

Flatmark, Kjersti ;

Lyng, Heidi ;

Calzada, Maria J. ;

del Peso, Luis ;

Landazuri, Manuel O. ;

Goerlach, Agnes ;

Flamm, Hubert ;

Kieninger, Jochen ;

Urban, Gerald ;

Weltin, Andreas ;

Singleton, Dean C. ;

Haider, Syed ;

Buffa, Francesca M. ;

Harris, Adrian L. ;

Scozzafava, Andrea ;

Supuran, Claudiu T. ;

Moser, Isabella ;

Jobst, Gerhard ;

Busk, Morten ;

Toustrup, Kasper ;

Overgaard, Jens ;

Alsner, Jan ;

Pouyssegur, Jacques ;

Chiche, Johanna ;

Mazure, Nathalie ;

Marchiq, Ibtissam ;

Parks, Scott ;

Ahmed, Afshan ;

Ashcroft, Margaret ;

Pastorekova, Silvia ;

Cao, Yihai ;

Rouschop, Kasper M. ;

Wouters, Brad G. ;

Koritzinsky, Marianne ;

Mujcic, Hilda ;

Cojocari, Dan .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2015, 30 (05) :689-721

[42] A short history of SHELX [J].

Sheldrick, George M. .

ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES, 2008, 64 :112-122

[43] Advances in structure-based drug discovery of carbonic anhydrase inhibitors [J].

Supuran, Claudiu T. .

EXPERT OPINION ON DRUG DISCOVERY, 2017, 12 (01) :61-88

[44] Legionella pneumophila Carbonic Anhydrases: Underexplored Antibacterial Drug Targets [J].

Supuran, Claudiu T. .

PATHOGENS, 2016, 5 (02)

[45] New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences [J].

Supuran, Claudiu T. ;

Capasso, Clemente .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2016, 31 (06) :1254-1260

[46] Structure and function of carbonic anhydrases [J].

Supuran, Claudiu T. .

BIOCHEMICAL JOURNAL, 2016, 473 :2023-2032

[47] Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors [J].

Supuran, Claudiu T. .

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2016, 12 (04) :423-431

[48] Acetazolamide for the treatment of idiopathic intracranial hypertension [J].

Supuran, Claudiu T. .

EXPERT REVIEW OF NEUROTHERAPEUTICS, 2015, 15 (08) :851-856

[49] Carbonic anhydrase inhibitors: an editorial [J].

Supuran, Claudiu T. .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2013, 23 (06) :677-679

[50] Carbonic anhydrases [J].

Supuran, Claudiu T. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (06) :1377-1378

← 1 2 3 4 5 6 →