Effects of new 5-amino-1,3,4-thiadiazole-2-sulfonamide derivatives on human carbonic anhydrase isozymes

Kasımoğulları, Rahmi; Bülbül, Metín; Günhan, Hatice; Güleryüz, Hülya

doi:10.1016/j.bmc.2009.03.048

Cited by 26 publications

(30 citation statements)

References 32 publications

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“…Inhibition of CA9 and CA12 esterase activity by AZA CA9 and CA12 esterase activity was inhibited by the wellcharacterized carbonic anhydrase inhibitor AZA in a dosedependent manner with an IC 50 of 0.14 mM ± 0.1 and 0.27 mM ± 0.1, respectively (Figure 1), in agreement with the published data on CA1 and CA2 33,34 A detailed kinetic characterisation of CA9 and CA12 esterase activity with and without AZA is presented in supplementary material ( Figure S1 and Table S2). …”

Section: Resultssupporting

confidence: 90%

“…We could confirm that CA9 and CA12 have esterase activity, which can be inhibited by AZA in a dose-dependent manner with IC 50 values similar to the ones published for CA1 and CA2 33,34 . We were able to confirm that MSC8, MSC12 and 4AB9 antibodies specifically bound to CA9, while the antibody 6A10 bound only to CA12.…”

Section: Discussionsupporting

confidence: 85%

“…These differences between the esterase and hydratase IC 50 values could be ascribed to the use of recombinant human CA9 and CA12 for the present esterase activity assays, whereas the published hydratase activity assays were performed with cell derived membrane fractions containing human CA9 and CA12. In addition, it has been shown that the esterase and hydratase IC 50 values may not have the best correlation even with the same compound for a particular CA isoform 33,35 . Moreover, IC 50 values are generally very dependent on several experimental conditions such as the enzyme and substrate concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Using the IC 50 values of a series of small molecule compounds on CA1 and CA2 isoforms from literature, we demonstrated that the hydratase and esterase IC 50 values have a correlation. However, the correlation is low having several outliers with varying IC 50 values for the same compound on a given CA isoform, and in addition, the IC 50 values of a compound also vary depending on the targeted CA isoform 33,35 . Such variations in IC 50 values suggest that the IC 50 values of a given compound do not necessarily have to be identical for both esterase and hydratase activity of a particular carbonic anhydrase isoform.…”

Section: Discussionmentioning

confidence: 99%

“…We analyzed the published IC 50 values of a series of small molecule compounds (Table 1) by plotting the correlation between their hydratase and esterase IC 50 values on CA1 ( Figure 7A) and on CA2 ( Figure 7B) 33,35 . The IC 50 values of these compounds (Table 1) showed relatively low correlation between hydratase and esterase activities, R 2 ¼ 0.61 for CA1 isoform ( Figure 7A) and R 2 ¼ 0.65 for CA2 isoform ( Figure 7B).…”

Section: Comparison Of Hydratase and Esterase Activitiesmentioning

confidence: 99%

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Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

Uda

Seibert

Stenner

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) were proposed as potential targets for cancer therapy more than 20 years ago. However, to date, there are only very few antibodies that have been described to specifically target CA9 and CA12 and also block the enzymatic activity of their targets. One of the early stage bottlenecks in identifying CA9-and CA12-inhibiting antibodies has been the lack of a high-throughput screening system that would allow for rapid assessment of inhibition of the targeted carbon dioxide hydratase activity of carbonic anhydrases. In this study, we show that measuring the esterase activity of carbonic anhydrase offers a robust and inexpensive screening method for identifying antibody candidates that block both hydratase and esterase activities of carbonic anhydrase's. To our knowledge, this is the first implementation of a facile surrogate-screening assay to identify potential therapeutic antibodies that block the clinically relevant hydratase activity of carbonic anhydrases.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Hydratase and Esterase Activitiesmentioning

confidence: 99%

See 3 more Smart Citations

Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

Uda

Seibert

Stenner

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones

2009

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An unprecedented copper-catalyzed intramolecular amidation of substituted 4-iodopyrazoles generated either via Baylis-Hillman or Horner-Wadsworth-Emmons chemistry for the synthesis of pyrazoloA C H T U N G T R E N N U N G [4,3-b]pyridine-5-ones is described. In addition, the effect of the stereochemistry of the acrylamide on the cross-coupling reaction has been investigated and it is demonstrated that only the Z-isomer is favoured to undergo the intramolecular cyclization.

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Synthesis, molecular docking analysis, drug‐likeness evaluation, and inhibition potency of new pyrazole‐3,4‐dicarboxamides incorporating sulfonamide moiety as carbonic anhydrase inhibitors

Özkul,

Tunca,

Mert

et al. 2024

J Biochem & Molecular Tox

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A series of novel pyrazole‐dicarboxamides were synthesized from pyrazole‐3,4‐dicarboxylic acid chloride and various primary and secondary sulfonamides. The structures of the new compounds were confirmed by FT‐IR, 1H‐NMR, 13C‐NMR, and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.024−0.496 µM for hCA I and 0.006−5.441 µM for hCA II. Compounds 7a and 7i showed nanomolar level of inhibition of hCA II, and these compounds exhibited high selectivity for this isoenzyme. Molecular docking studies were performed between the most active compounds 7a, 7b, 7i, and the reference inhibitor AAZ and the hCAI and hCAII to investigate the binding mechanisms between the compounds and the isozymes. These compounds showed better interactions than the AAZ. ADMET and drug‐likeness analyses for the compounds have shown that the compounds can be used pharmacologically in living organisms.

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Effects of new 5-amino-1,3,4-thiadiazole-2-sulfonamide derivatives on human carbonic anhydrase isozymes

Cited by 26 publications

References 32 publications

Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity

First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones

Synthesis, molecular docking analysis, drug‐likeness evaluation, and inhibition potency of new pyrazole‐3,4‐dicarboxamides incorporating sulfonamide moiety as carbonic anhydrase inhibitors

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