Differential<i>in vitro</i>inhibition effects of some antibiotics on tumor associated carbonic anhydrase isozymes of hCA-IX and hCA-XII

Ozensoy, Ozen; Arslan, Oktay; Köçkar, Feray

doi:10.1080/14756360701731957

Cited by 7 publications

(6 citation statements)

References 37 publications

(27 reference statements)

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“…It has been reported that the CA XV isoform is not expressed in humans or in other primates, but it is abundant in rodents and other vertebrates 14,15 . These enzymes catalyze a very simple but critically important physiological reaction, rapid interconversion of carbon dioxide and water into protons and bicarbonate ions, in many physiological/pathological processes open up widespread opportunities for the development of diverse, specific inhibitors for clinical applications 16,17 . In addition to this physiological reaction, the reversible hydration of CO 2 to bicarbonate, CAs catalyze several other reactions, such as the hydration of cyanate or cyanamide to carbamic acid, or urea, the aldehyde hydration to gem-diols, the hydrolysis of carboxylic, or sulfonic and some others 18,19 .…”

mentioning

confidence: 99%

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Kilicaslan

Arslan

Ruya

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a-l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC 50 ¼ 0.35 mM; Ki: 0.33 mM) for hCA I and hCA II.

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mentioning

confidence: 99%

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Kilicaslan

Arslan

Ruya

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In literature, it has been reported that IC 50 values of sodium ampicillin were 0.385 mM on hCA-I and 0.774 mM on hCA-II (Beydemir et al, 2000). Ozensoy et al (2008) reported that cefuroxime axetil for hCA I and hCA II isozymes as IC 50 value of 2.92 Â 10 À5 and 2.12 Â 10 À5 mM, respectively. Recently, our group determined that the IC 50 concentrations of dexketoprofen trometamol and dexamethasone sodium phosphate on hCA I were 683 and 4250 mM and for hCA II 950 and 6200 mM respectively (Gokce et al, 2012).…”

Section: Resultsmentioning

confidence: 98%

Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors

Erzengin

Bilen

Ergün

et al. 2013

Archives of Physiology and Biochemistry

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The antipsychotic drugs currently used to treat schizophrenia can be divided into two distinct classes, typical and atypical antipsychotics. Many drug molecules are enzyme inhibitors that bind reversibly or irreversibly to their target through intermolecular interactions. That's why enzyme inhibition studies are an important issue for drug design and biochemical applications. In this study, in vitro inhibition effect of some antipsychotic drugs on the purified carbonic anhydrase (CA) I and II isoenzymes were investigated by using CO2 as a substrate. CA I and II were purified from human erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The results showed that all the drugs inhibited the cytosolic carbonic anhydrases enzyme activity in a concentration-dependent fashion. Among the studied drugs, aripiprazole and pramipexole were found to be the most active one for hCA I (IC50: 3.64 and 5.37 μM) and hCA II (IC50: 4.16 and 4.81 μM) activity, respectively.

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“…15,16f An interesting example among the literature-confirmed predictions is the inhibitory activity of amoxicillin (IC 50 = 3.47 μM) on carbonic anhydrase XII. 34 This prediction illustrates the ability of BioSEA to capture bioisosterism, since it was mostly based on the biological similarity to compounds in the training set such as 4-sulfamoylbenzoic acid, sulpiride, or indapamide, all of them sulfonamides. Though structurally unrelated to amoxicillin, all of these compounds have in common a chemical group that is able to interact with the zinc atom in the enzyme's active site (carboxylate or sulfonamide moieties, respectively).…”

Section: Acs Chemical Biologymentioning

confidence: 84%

“…An interesting example among the literature-confirmed predictions is the inhibitory activity of amoxicillin (IC 50 = 3.47 µM) on carbonic anhydrase XII 39 . This prediction illustrates the ability of BIOSEA to capture bioisosterism, since it was mostly based in the biologically similarity to compounds in the training set such as 4-sulfamoylbenzoic acid, sulpiride or indapamide, all of them sulfonamides.…”

Section: Biosea Can Identify New Targets For Old Compoundsmentioning

confidence: 92%

Aggregated Compound Biological Signatures Facilitate Phenotypic Drug Discovery and Target Elucidation

et al. 2016

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Predicting the cellular response of compounds is a challenge central to the discovery of new drugs. Compound biological signatures have risen as a way of representing the perturbation produced by a compound in the cell. However, their ability to encode specific phenotypic information and generating tangible predictions remains unknown, mainly because of the inherent noise in such data sets. In this work, we statistically aggregate signals from several compound biological signatures to find compounds that produce a desired phenotype in the cell. We exploit this method in two applications relevant for phenotypic screening in drug discovery programs: target-independent hit expansion and target identification. As a result, we present here (i) novel nanomolar inhibitors of cellular division that reproduce the phenotype and the mode of action of reference natural products and (ii) blockers of the NKCC1 cotransporter for autism spectrum disorders. Our results were confirmed in both cellular and biochemical assays of the respective projects. In addition, these examples provided novel insights on the information content and biological significance of compound biological signatures from HTS, and their applicability to drug discovery in general. For target identification, we show that novel targets can be predicted successfully for drugs by reporting new activities for nimedipine, fluspirilene, and pimozide and providing a rationale for repurposing and side effects. Our results highlight the opportunities of reusing public bioactivity data for prospective drug discovery, including scenarios where the effective target or mode of action of a particular molecule is not known, such as in phenotypic screening campaigns.

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Differentialin vitroinhibition effects of some antibiotics on tumor associated carbonic anhydrase isozymes of hCA-IX and hCA-XII

Cited by 7 publications

References 37 publications

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors

Aggregated Compound Biological Signatures Facilitate Phenotypic Drug Discovery and Target Elucidation

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