Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors

Sączewski, Franciszek; Sławiński, Jarosław; Kornicka, Anita; Brzozowski, Z; Pomarnacka, E; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T.

doi:10.1016/j.bmcl.2006.06.064

Cited by 46 publications

(21 citation statements)

References 31 publications

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“…Another sophisticated strategy was used to generate hypoxia-activatable inhibitors. Different 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones showed consistently increased inhibitory power (52.8-to 243-fold) over the corresponding oxidized (S-S type) derivatives (Saczewski et al 2006). The best representatives out of these differentially acting derivatives can serve as lead compounds for further development of CA IX-specific inhibitors with therapeutic potential against cancer.…”

Section: Ca IX Targeting Through Inhibitors Of Catalytic Activitymentioning

confidence: 97%

Carbonic Anhydrase IX: From Biology to Therapy

Pastoreková¹,

Supuran²

2013

Hypoxia and Cancer

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Growing tumor tissues develop a stressful microenvironment characterized by hypoxia and acidosis. Tumor cells can survive these stresses via induction of adaptive transcriptional changes mediated primarily by the hypoxia-inducible factor (HIF), and via stimulation of ion transport machinery maintaining normal intracellular pH. In addition, through these adaptive responses tumor cells acquire new features endowing them with selective advantage in migration, invasion, metastasis, and resistance to therapy. Carbonic anhydrase IX (CA IX), a highly active cancer-related carbonic anhydrase isoform, is linked to both hypoxia, as a direct transcriptional target of HIF, and acidosis, as a component of mechanisms that facilitate ion transport across the plasma membrane and thereby counteract the intracellular accumulation of acidic metabolic products. Expression pattern of CA IX in human tumors reflects the activation of the HIF pathway by physiologic hypoxia, genetic defects, and/or oncogenic events. Moreover, CA IX plays an active role not only in pH regulation but also in cell migration and invasion. Thus, it is often exploited and/or investigated as an intrinsic marker of hypoxia, a prognostic indicator, and a therapeutic target for antibodies or inhibitors of the enzyme activity. It is believed that these CA IXtargeted therapeutic approaches can mediate the selective killing of CA IX-positive cells or sensitize tumor cells to conventional treatment modalities. In addition, both

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Section: Ca IX Targeting Through Inhibitors Of Catalytic Activitymentioning

confidence: 97%

Carbonic Anhydrase IX: From Biology to Therapy

Pastoreková¹,

Supuran²

2013

Hypoxia and Cancer

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“…At least 13 enzymatically active isoforms have been discovered in higher vertebrates [12e15]. CAs are involved in pH regulation, secretion of electrolytes, respiration [17,18], biosynthetic reactions which require CO 2 /bicarbonate as substrate such as gluconeogenesis, lipogenesis, ureagenesis, and pyrimidines synthesis among others [19]. Other roles for these enzymes were highlighted, such as calcification and bone resorption [19].…”

Section: Introductionmentioning

confidence: 99%

In vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety

Ghorab

Ragab

Heiba

et al. 2010

European Journal of Medicinal Chemistry

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“…Currently, there is significant interest in the discovery and development of novel sulfonamides for the treatment of cancer and HIV infection [2][3][4][5]. As part of extensive research program on the synthesis of compound containing 2-thiobenzenesulfonamide scaffold, several series of novel sulfonamides with remarkable anticancer activity [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], anti-HIV activity [14], [20][21][22][23][24][25][26][27][28][29], or carbonic anhydrase inhibitors [30][31][32] were discovered in our laboratories. In the course of study on the synthesis of heterocyclic compounds bearing sulfonamide moiety, we developed new methods for preparation of novel series of 3-pyridinesulfonamides [33][34][35][36] and found that numerous sulfonamides of type I [35] and II [36] (Fig.…”

Section: Introductionmentioning

confidence: 99%

On the Reaction Products of 4‐Substituted 3‐Pyridinesulfonamides with Some Benzenesulfonyl Chloride Derivatives

Brzozowski

Sławiński

Szafrański

2013

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).The reactions of 4-substituted 3-pyridinesulfonamides 1a-e with benzenesulfonyl chlorides 2a-f in acetonitrile were investigated. Depending on the structure of arylsulfonyl chlorides and the reaction conditions the following four types of products were obtained in good yields: 3-sulfamoyl-4-R-1-arylpyridinium chlorides 3-8; 1,10-bis(3-nitrobenzenesulfonylimino)deca-2,4,6,8-tetraene-2,9-disulfonamides 9-12; 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides 13-14; and 4-methoxy-3-[N-(2,5-dichlorophenyl)sulfonyl] sulfonamidates 15 and 16. The mechanisms of these reactions were discussed.

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Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors

Cited by 46 publications

References 31 publications

Carbonic Anhydrase IX: From Biology to Therapy

Carbonic Anhydrase IX: From Biology to Therapy

In vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety

On the Reaction Products of 4‐Substituted 3‐Pyridinesulfonamides with Some Benzenesulfonyl Chloride Derivatives

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