Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action

Puşcaş, I; Ifrim, M; Maghiar, Teodor; Coltâu, Marcela; Domuţa, Gabriela; Baican, M; Hecht, A

doi:10.5414/cpp39265

Cited by 6 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Flurbiprofen is a weak carbonic anhydrase II inhibitor whereas ibuprofen and indomethacin are even much less active against this enzyme [ 117 ]. In two papers by Puscas et al indomethacin was said to be an agonist of CA, but this conclusion was reached after indomethacin limited inhibitory effect of acetazolamide on carbonic anhydrase [ 118 , 119 ] and it was uncertain whether it was indeed CA agonist or just weaker than acetazolamide CA inhibitor competing for a binding site. Acetylsalicylic acid (ASA) is a noncompetitive carbonic anhydrase II inhibitor [ 120 ], but this activity may be associated with adjusting environmental pH by ASA [ 121 ].…”

Section: Platelet Carbonic Anhydrasementioning

confidence: 99%

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Jakubowski

Szahidewicz-Krupska

Doroszko

2018

BioMed Research International

View full text Add to dashboard Cite

Carbonic anhydrases constitute a group of enzymes that catalyse reversible hydration of carbon dioxide leading to the formation of bicarbonate and proton. The platelet carbonic anhydrase II (CAII) was described for the first time in the '80s of the last century. Nevertheless, its direct role in platelet physiology and pathology still remains poorly understood. The modulation of platelet CAII action as a therapeutic approach holds promise as a novel strategy to reduce the impact of cardiovascular diseases. This short review paper summarises the current knowledge regarding the role of human CAII in regulating platelet function. The potential future directions considering this enzyme as a potential drug target and important pathophysiological chain in platelet-related disorders are described.

show abstract

Section: Platelet Carbonic Anhydrasementioning

confidence: 99%

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Jakubowski

Szahidewicz-Krupska

Doroszko

2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Furthermore, it has also been reported that NSAIDs indeed compete with thyroid hormone binding in vivo [54,55]. Similarly, based on the observed connection between the two neighboring modules (CA module and fatty acid module) due to celecoxib (PubChem CID: 2662), a selective COX2 inhibitor with nanomolar activity against the carbonic anhydrase [56], we successfully verified a hidden interaction of alpha-CA-I-II-III-XIII domain with indomethacin, a ligand of the PES domain [57,58]. …”

Section: Resultsmentioning

confidence: 94%

Characterizing protein domain associations by Small-molecule ligand binding

Li¹,

Cheng²,

Wang³

et al. 2012

J Proteome Sci Comput Biol

View full text Add to dashboard Cite

Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing.

show abstract

“…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). Puscas et al (2001) reported that indomethacin, in vitro and in vivo, induces an increase in erythrocyte CA I and CA II activity. In humans, an increase or decrease in erythrocyte CA II activity is correlated with an increase or decrease in gastric acid secretion.…”

Section: Resultsmentioning

confidence: 99%

Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors

Erzengin

Bilen

Ergün

et al. 2013

Archives of Physiology and Biochemistry

View full text Add to dashboard Cite

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.

show abstract

Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action

Cited by 6 publications

References 0 publications

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Characterizing protein domain associations by Small-molecule ligand binding

Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors

Contact Info

Product

Resources

About