Carbonic anhydrase IX as a novel candidate in liquid biopsy

Guler, Ozen Ozensoy; Supuran, Claudiu T.; Capasso, Clemente

doi:10.1080/14756366.2019.1697251

Cited by 20 publications

(5 citation statements)

References 88 publications

(103 reference statements)

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“…The CA superfamily is grouped into eight genetically distinct families (or classes), named with the Greek letters α, β, γ, δ, ζ, η, θ, and ι [13][14][15]30,31]. In mammalian, for example, 15 CAs are expressed, 12 of which are catalytically active, and all belong to the α-class [9,16,[32][33][34][35][36][37]. It is interesting to stress that the genome of most pathogens does not encode for a α-CA [12][13][14]34,38,39].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for Escherichia coli Life Cycle

Prete

Luca

Bua

et al. 2020

IJMS

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Proteins are relevant antimicrobial drug targets, and among them, enzymes represent a significant group, since most of them catalyze reactions essential for supporting the central metabolism, or are necessary for the pathogen vitality. Genomic exploration of pathogenic and non-pathogenic microorganisms has revealed genes encoding for a superfamily of metalloenzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the physiologically crucial reversible reaction of the carbon dioxide hydration to bicarbonate and protons. Herein, we investigated the sulfonamide inhibition profile of the recombinant β-CA (CynT2) identified in the genome of the Gram-negative bacterium Escherichia coli. This biocatalyst is indispensable for the growth of the microbe at atmospheric pCO2. Surprisingly, this enzyme has not been investigated for its inhibition with any class of CA inhibitors. Here, we show that CynT2 was strongly inhibited by some substituted benzene-sulfonamides and the clinically used inhibitor sulpiride (KIs in the range of 82–97 nM). This study may be relevant for identifying novel CA inhibitors, as well as for another essential part of the drug discovery pipeline, such as the structure–activity relationship for this class of enzyme inhibitors.

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Section: Introductionmentioning

confidence: 99%

The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for Escherichia coli Life Cycle

Prete

Luca

Bua

et al. 2020

IJMS

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“…Hence, many pharmaceutical uses have notable goals for a variety of CA isoforms, including antiglaucoma drugs, anticonvulsant factors/diagnostic, diuretics, antiobesity, and antitumor tools [ 59 , 60 ]. For instance, inhibitors of the hCAs IX and XII isozymes have been used as antitumor and antimetastatic agents [ 61 , 62 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Bromophenol with Diaryl Methanes—Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase

et al. 2022

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In this work, nine new bromophenol derivatives were designed and synthesized. The alkylation reactions of (2-bromo-4,5-dimethoxyphenyl)methanol (7) with substituted benzenes 8–12 produced new diaryl methanes 13–17. Targeted bromophenol derivatives 18–21 were synthesized via the O-Me demethylation of diaryl methanes with BBr3. Moreover, the synthesized bromophenol compounds were tested with some metabolic enzymes such as acetylcholinesterase (AChE), carbonic anhydrase I (CA I), and II (CA II) isoenzymes. The novel synthesized bromophenol compounds showed Ki values that ranged from 2.53 ± 0.25 to 25.67 ± 4.58 nM against hCA I, from 1.63 ± 0.11 to 15.05 ± 1.07 nM against hCA II, and from 6.54 ± 1.03 to 24.86 ± 5.30 nM against AChE. The studied compounds in this work exhibited effective hCA isoenzyme and AChE enzyme inhibition effects. The results show that they can be used for the treatment of glaucoma, epilepsy, Parkinson’s as well as Alzheimer’s disease (AD) after some imperative pharmacological studies that would reveal their drug potential.

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“…Inhibition of CAs has important pharmacological implications, for example, in the treatment of glaucoma, epilepsy, acute mountain sickness, and, more recently, even cancer [ 13 , 14 , 15 , 16 , 17 ]. CAs may also be useful as markers for cancer diagnosis [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney

Lee

Boron

Occhipinti

2023

IJMS

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Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO2) and water into bicarbonate (HCO3−) and protons (H+), thereby influencing pH, are near the core of virtually all physiological processes in the body. In the kidneys, soluble and membrane-associated CAs and their synergy with acid–base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3− in specific nephron segments. Among these transporters are the Na+-coupled HCO3− transporters (NCBTs) and the Cl−-HCO3− exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO3−“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO32− rather than HCO3− and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO3−” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO3− reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3−, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32− transport by NCBTs, however, we hypothesize that the role of membrane-associated CAs is not the appreciable production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.

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Carbonic anhydrase IX as a novel candidate in liquid biopsy

Cited by 20 publications

References 88 publications

The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for Escherichia coli Life Cycle

The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for Escherichia coli Life Cycle

Synthesis of Novel Bromophenol with Diaryl Methanes—Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase

Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney

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