Carbonic Anhydrase and Biomarker Research: New Insights

Lionetto, Maria Giulia

doi:10.3390/ijms24119687

Cited by 6 publications

(2 citation statements)

References 18 publications

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“…Carbonic anhydrases (CA) represent a family of ∼15 Zn-metalloenzymes that play a pivotal role in health and disease as they are involved in several physiological processes, including pH regulation, respiration, electrolyte transport, metabolism, bone resorption, and calcification. 1 , 2 While CA IX and XII are cell membrane proteins that are expressed in various tissues and hold potential as biomarkers for certain cancers, 1 , 3 the CA present in red blood cells (RBCs) is a monomeric ∼30 kDa Zn-metalloprotein that is primarily responsible for mediating the transport of the waste product CO 2 from internal organs to the lungs. 4 While human RBCs contain at least 1587 cytosolic proteins, 5 the most abundant protein therein is haemoglobin (Hb, ∼5.5 mM), followed by the second most abundant protein CA I, 6 which is present at concentrations of ∼12 mg/g of Hb.…”

Section: Introductionmentioning

confidence: 99%

Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro

Doroudian,

Gailer

2024

Metallomics

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Red blood cells (RBCs) constitute ∼50% of the bloodstream and represent an important target for environmental pollutants and bacterial/viral infections, which can result in their rupture. In addition, diseases such as sickle cell anaemia and paroxysmal nocturnal haemoglobinuria can also result in the rupture of RBCs, which can be potentially life-threatening. With regard to the release of cytosolic metalloproteins from RBCs into the blood-organ system, the biochemical fate of haemoglobin is rather well understood, while comparatively little is known about another highly abundant Zn-metalloprotein, carbonic anhydrase (CA I). To gain insight into the interaction of CA I with human blood plasma constituents, we have employed a metallomics tool comprised of size-exclusion chromatography (SEC) coupled online with an inductively coupled plasma atomic emission spectrometer (ICP-AES), which allows to simultaneously observe all Cu, Fe, and Zn-metalloproteins. After the addition of CA I to human blood plasma incubated at 37°C, the SEC-ICP-AES analysis using phosphate buffered saline (pH 7.4) after 5 min, 1 h, and 2 h revealed that CA I eluted after all endogenous Zn-metalloproteins in the 30 kDa range. Matrix-assisted laser desorption-time of flight mass spectrometry analysis of the collected Zn-peak confirmed that CA I eluted from the column intact. Our in vitro results suggest that CA I released from RBCs to plasma remains free and may be actively involved in health-relevant adverse processes that unfold at the bloodstream-endothelial interface, including atherosclerosis and vision loss.

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Section: Introductionmentioning

confidence: 99%

Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro

Doroudian,

Gailer

2024

Metallomics

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“…Currently 15 CAs have been discovered and described in humans and are involved in several physiological and biochemical processes, such as pH homeostasis, gluconeogenesis, liquid secretion, and tumorgenicity. The active site of human CAs (hCAs) contains zinc ions in a tetrahedral geometric shape, coordinated by three amino acid residues, H94, H96, and H119, in addition to a H 2 O molecule or OH – ion. − The hCA IX and hCA XII isoenzymes have been deeply studied due to their important role in cancer cell survival. − Although small metabolic changes are tolerated in cancer cells, strong pH control is necessary for their survival and proliferation . Hydrogen carbonate ions, which are important pH buffers, are imported by transporters such as Cl – /HCO 3 – anion exchanger and Na + /HCO 3 – co-transporter, consuming cytosolic protons to give a new molecule of CO 2 which leaves the cytoplasm to be hydrated by hCA IX and XII .…”

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confidence: 99%

Discovery of a New Class of 1-(4-Sulfamoylbenzoyl)piperidine-4-carboxamides as Human Carbonic Anhydrase Inhibitors

Moi,

Vittorio,

Angeli

et al. 2024

ACS Med. Chem. Lett.

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A series of 1-(4-sulfamoylbenzoyl)piperidine-4-carboxamides deriving from substituted piperazines/benzylamines was designed, synthesized, and tested on human carbonic anhydrase (hCA). The inhibitory activity of the new sulfonamides was analyzed using acetazolamide (AAZ) as a standard inhibitor against hCA I, II, IX, and XII. Several sulfonamides showed both inhibitory activity at low nanomolar concentrations and selectivity against the cytosolic hCA II isoform, and the same trend was observed on the tumor-associated hCA IX and XII. The benzenesulfonamido carboxamides 11 and 15 were the most potent of the piperazino- and benzylamino-based series, respectively. Docking and molecular dynamics studies related the high selectivity of compound 11 toward the tumor-associated hCA isoforms to its capability to participate in favorable interactions within hCA IX and hCA XII active sites, whereas no such interactions were detected within both hCA I and hCA II isoforms.

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Novel benzene sulfonamides with acetylcholinesterase and carbonic anhydrase inhibitory actions

El Ati,

Öztaşkın,

Çağan

et al. 2024

Archiv der Pharmazie

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A series of benzene sulfonamides 15–26 were synthesized and determined for their in vitro and in silico inhibitory profiles toward acetylcholinesterase (AChE) and carbonic anhydrases (CAs). Commercially available 3,4‐dimethoxytoluene was reacted with chlorosulfonic acid to furnish benzene sulfonyl chloride derivatives. The reaction of substituted benzene sulfonyl chloride with some amines also including (±)‐α‐amino acid methyl esters afforded a series of novel benzene sulfonamides. In this study, the enzyme inhibition abilities of these compounds were evaluated against AChE and CAs. They exhibited a highly potent inhibition ability on AChE and ‐CAs (Ki values are in the range of 28.11 ± 4.55 nM and 145.52 ± 28.68 nM for AChE, 39.20 ± 2.10 nM to 131.54 ± 12.82 nM for CA I, and 50.96 ± 9.83 nM and 147.94 ± 18.75 nM for CA II). The present newly synthesized novel benzene sulfonamides displayed efficient inhibitory profiles against AChE and CAs, and it is anticipated that they may emerge as lead molecules for some diseases including glaucoma, epilepsy, and Alzheimer's disease.

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Carbonic Anhydrase and Biomarker Research: New Insights

Abstract: Carbonic anhydrase (CA) is a widespread metalloenzyme with eight genetically distinct families catalyzing the reversible hydration of CO2 to HCO3− and H+ [...]

Cited by 6 publications

References 18 publications

Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro

Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro

Discovery of a New Class of 1-(4-Sulfamoylbenzoyl)piperidine-4-carboxamides as Human Carbonic Anhydrase Inhibitors

Novel benzene sulfonamides with acetylcholinesterase and carbonic anhydrase inhibitory actions

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