4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII

Dudutienė, Virginija; Zubrienė, Asta; Smirnov, Alexander; Gylytė, Joana; Timm, David D.; Manakova, E.; Gražulis, S.; Matulis, Daumantas

doi:10.1016/j.bmc.2013.01.008

Cited by 70 publications

(76 citation statements)

References 53 publications

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“…1, were tested as potential inhibitors of CA VB by measuring their binding affinity using fluorescent thermal shift assay (FTSA). Compound synthesis and affinities to several CA isoforms have been previously described [47]. Dissociation constants for the compound binding to CA VB are listed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…The chemical synthesis and binding of compounds 1-8 to several CA isoforms has been previously described [47], other compounds obtained from Sigma-Aldrich and Alpha Aesar.…”

Section: Chemistrymentioning

confidence: 99%

“…1 Chemical structures of CA inhibitors discussed in this manuscript. Their chemical synthesis and binding to several other CA isoforms has been previously described [47] Intrinsic dissociation constants of the compounds are also listed for CA VB (37°C)…”

Section: Inhibitor Binding To Ca Vb By Itcmentioning

confidence: 99%

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Thermodynamic characterization of human carbonic anhydrase VB stability and intrinsic binding of compounds

Kasiliauskaitė

Časaitė

Juozapaitienė

et al. 2015

J Therm Anal Calorim

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The thermodynamics of low molecular weight synthetic sulfonamide inhibitor binding to carbonic anhydrase (CA) VB was determined by the isothermal titration calorimetry (ITC) and the fluorescent thermal shift assay (FTSA). ITC provided the enthalpic and entropic contributions to the binding affinity of ethoxzolamide to CA VB. FTSA is a high-throughput assay that measures protein thermal stabilization by added ligands. FTSA enabled determination of extremely high affinity of several compounds binding to CA VB. CA VB is one of two isoforms that are expressed in mitochondria, participate in carbon metabolism and pH homeostasis and are implicated in diseases such as obesity. Therefore CA VB is a drug target. Here a series of para-substituted tetrafluoro benzenesulfonamides were investigated as high affinity inhibitors of CA VB. Thermodynamic equilibrium binding measurements such as ITC and FTSA provide only the observed parameters. Dissection of binding-linked reactions is necessary to obtain the intrinsic parameters that in turn could be correlated with the chemical structure of the inhibitors. Intrinsic dissociation constants of the inhibitors were estimated and they reached 1 pM, one of the strongest binding reactions observed between any protein-ligand binding.

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Section: Resultsmentioning

confidence: 99%

“…The chemical synthesis and binding of compounds 1-8 to several CA isoforms has been previously described [47], other compounds obtained from Sigma-Aldrich and Alpha Aesar.…”

Section: Chemistrymentioning

confidence: 99%

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Thermodynamic characterization of human carbonic anhydrase VB stability and intrinsic binding of compounds

Kasiliauskaitė

Časaitė

Juozapaitienė

et al. 2015

J Therm Anal Calorim

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“…Transformants were cultured in Luria Bertani (LB) medium, containing 100 mg/ml ampicillin, 34 mg/ml chloramphenicol and grown at 37 C and 220 rpm for 16 h. The expression of CA XII was induced with 1 mM isopropyl b-D-thiogalactoside (IPTG) and 0.5 mM ZnSO 4 . The culture was grown for 4 h at 30 C and 220 rpm. The cells were harvested, mixed with lysis buffer (20 mM Hepes, 0.1% Triton X-100, 0.15 M NaCl, (pH 8.5) and 1 mM PMSF) and disrupted by sonication.…”

Section: Production Of Recombinant Ca XIImentioning

confidence: 99%

“…Recombinant CA I, CA II, CA VII and CA XIII were expressed in E. coli and purified as described previously 30 . Recombinant CA XII was expressed in mammalian cells and purified as described previously 31 .…”

Section: Production Of Recombinant Ca XIImentioning

confidence: 99%

Monoclonal antibodies raised against 167–180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity

Dekaminaviciute

Kairys

Zilnyte

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Human carbonic anhydrase XII (CA XII) is a single-pass transmembrane protein with an extracellular catalytic domain. This enzyme is being recognized as a potential biomarker for different tumours. The current study was aimed to generate monoclonal antibodies (MAbs) neutralizing the enzymatic activity of CA XII. Bioinformatics analysis of CA XII structure revealed surface-exposed sequences located in a proximity of its catalytic centre. Two MAbs against the selected antigenic peptide spanning 167-180 aa sequence of CA XII were generated. The MAbs were reactive with recombinant catalytic domain of CA XII expressed either in E. coli or mammalian cells. Inhibitory activity of the MAbs was demonstrated by a stopped flow CO 2 hydration assay. The study provides new data on the surface-exposed linear CA XII epitope that may serve as a target for inhibitory antibodies with a potential immunotherapeutic application. KeywordsHuman carbonic anhydrase XII, inhibition of enzymatic activity, monoclonal antibodies History

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Microfluidic Encapsulation of Prickly Zinc‐Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy

Zhang

Liu

Wang

et al. 2017

Adv Healthcare Materials

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Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof-of-concept, Prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH-responsive polymer; and the surface has been modified with a novel synthesized ligand, 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication.

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4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII

Cited by 70 publications

References 53 publications

Thermodynamic characterization of human carbonic anhydrase VB stability and intrinsic binding of compounds

Thermodynamic characterization of human carbonic anhydrase VB stability and intrinsic binding of compounds

Monoclonal antibodies raised against 167–180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity

Microfluidic Encapsulation of Prickly Zinc‐Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy

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