Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII

Čapkauskaitė, Edita; Zubrienė, Asta; Smirnov, Alexander; Torresan, Jolanta; Kišonaitė, Miglė; Kazokaitė, Justina; Gylytė, Joana; Michailovienė, Vilma; Jogaite, Vaida; Manakova, E.; Gražulis, S.; Tumkevičius, Sigitas; Matulis, Daumantas

doi:10.1016/j.bmc.2013.09.029

Cited by 41 publications

(37 citation statements)

References 32 publications

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“…CA isozymes play vital physiological functions, such as respiration and acid‐base balance, bone resorption, electrolyte secretion, calcification, and biosynthetic reactions, which require HCO 3 − as a substrate, in all organisms . The majority of CA isozymes constitute targets for the design and development of CA inhibitors for clinical practices . It is well known that CA isozymes are effectively inhibited by aromatic, heterocyclic and inorganic sulfonamides as well as by metal complexing sulfonamides.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1‐Aminoindanes and Anilines

Akbaba

Bastem

Topal

et al. 2014

Archiv der Pharmazie

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Three 1-aminoindanes, four anilines and BnOH or t-BuOH were reacted with chlorosulfonyl isocyanate to give sulfamoyl carbamates. Pd-C catalysed hydrogenolysis reactions of carbamates or deprotection of the Boc group of the carbamates with CF3 CO2 H afforded seven novel sulfamides. Human carbonic anhydrase (hCA) isoenzymes I and II (hCA I and hCA II) were purified from fresh human blood erythrocytes with one-step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The inhibitory properties of the novel sulfamides on both isoenzymes were determined using the esterase activity with 4-nitrophenyl acetate (NPA) as substrate. The tested novel sulfamides derived from 1-aminoindanes and anilines effectively inhibited hCA I and II competitively in the nanomolar range. Among these compounds, the novel sulfamide derivative 17 showed the most potent inhibitory effect against hCA I (Ki : 153.88 nM), while sulfamide derivative 26 showed the highest inhibitory potential against hCA II (Ki : 117.80 nM).

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Section: Resultsmentioning

confidence: 99%

Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1‐Aminoindanes and Anilines

Akbaba

Bastem

Topal

et al. 2014

Archiv der Pharmazie

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“…The purification procedure has been described previously . The expression in E. coli and purification of the recombinant human CA VI has been previously reported .…”

Section: Methodsmentioning

confidence: 99%

Intrinsic binding of 4‐substituted‐2,3,5,6‐tetrafluorobenezenesulfonamides to native and recombinant human carbonic anhydrase VI

et al. 2015

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Carbonic anhydrase (CA) VI is a potential drug target for cariogenesis and cancer of the salivary gland. It is the only secreted human CA isozyme which is found in saliva and milk. Here, CA VI was expressed in bacterial and mammalian cell cultures and directly affinity‐purified from human saliva. The binding of 4‐substituted‐2,3,5,6‐tetrafluorobenezenesulfonamides to the native and recombinant CA VI from these three sources was compared. Interaction between the enzyme and inhibitors was determined by fluorescent thermal shift assay and isothermal titration calorimetry. The observed dissociation constants were the same within the error margin for all three CA VI preparations. The intrinsic binding parameters for the compounds were obtained by determining and dissecting the binding‐linked protonation reactions. Intrinsic thermodynamic parameters of binding arrange the compounds in a buffer‐ and pH‐independent manner. Intrinsic binding constants of nonfluorinated compounds were significantly stronger than those of fluorinated benzenesulfonamides. An opposite result was determined for the observed binding constants. The increase in observed affinity of the fluorinated compounds was due to the fluorine effect on diminishing the pKa of the compounds but not due to direct recognition of the protein. The temperature–stability profiles for recombinant and native CA VI were compared and showed that CA VI is more stable in slightly acidic than neutral conditions.

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“…As in CA II, AZM interacts with a Phe131 side chain, that is absent in CA XII, the position of ligand differs between two isoforms. CA XII was used for the comparison of binding of various compounds with different human CA isoforms in the search of isoform-specific inhibitors (Čapkauskaitė et al, 2013;Dudutienė et al, 2013Dudutienė et al, , 2014Dudutienė et al, , 2015Zubrienė et al, 2015).…”

Section: Ca XIImentioning

confidence: 99%

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

Linkuvienė

Zubrienė

Manakova

et al. 2018

Quart. Rev. Biophys.

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Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII

Cited by 41 publications

References 32 publications

Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1‐Aminoindanes and Anilines

Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1‐Aminoindanes and Anilines

Intrinsic binding of 4‐substituted‐2,3,5,6‐tetrafluorobenezenesulfonamides to native and recombinant human carbonic anhydrase VI

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

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