Carbonic anhydrase inhibitory properties of some uracil derivatives

Türkoğlu, Emir Alper; Şentürk, Murat; Supuran, Claudiu T.; Ekinci, Deniz

doi:10.1080/14756366.2016.1235043

Cited by 38 publications

(25 citation statements)

References 33 publications

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“…All reported diaminopteridine-benzenesulfonamide conjugates displayed low nanomolar range inhibition toward hCA IX while isoforms hCA I and hCA II were inhibited with high nanomolar range by these compounds. Diaminopteridine-benzenesulfonamide conjugates, containing NHCH 2 CH 2 (compound 200), as well as compound 201, and compound 202, showed selective inhibition for hCA IX over hCA I and hCA II (Figure 15).Conjugates 200,201, and 202 showed a K i value of 4.7, 2.5, and 3.7 nM, respectively, against hCA IX. These potent hCA IX inhibitors have also shown selectivity between 9.6-and 369-fold over hCA II and between 348-and 5829-fold over hCA I.…”

mentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

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188

166

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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mentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

Self Cite

188

166

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“…In an earlier report from our group, the inhibitory ability of compounds 2–9 on human carbonic anhydrase (hCA) was investigated 14 . Some of these uracil derivatives demonstrated good to moderate inhibition profiles against hCA I and hCA II 14 , 32 . Inhibitors of carbonic anhydrase (CA) have been carried out in many therapeutic applications, especially antiglaucoma activity.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies

Çavdar

Şentürk

Güney

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer’s disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives. The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Molecular docking and molecular dynamics (MD) simulations demonstrated the possible key interactions between the studied ligands and amino acid residues at different regions of the active sites of AChE and BuChE. Being diverse of the classical AChE and BuChE inhibitors, the investigated uracil derivatives may be used as lead molecules for designing new therapeutically effective enzyme inhibitors.

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“…In this context, it is possible that the observed effect of poly(I:C) could be a combined effect of PKR, RIG-I, MDA5 and TLR3. Interestingly, foscarnet and uracils, antiviral drugs and their derivatives, inhibit the activity of a variety of CAs in vitro (15,16) and CA inhibitors enhance the activity of a nucleo-polyhedrovirus (17). Gel-based recombinant CA IV application to full-thickness skin wounds in mice has been found to significantly improve wound re-epithelialization (18).…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 3 Agonist, Polyinosinic-polycytidylic Acid, Upregulates Carbonic Anhydrase II in Human Keratinocytes

Suri¹,

Verma²,

Schmidtchen³

2018

Acta Derm Venerol

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Carbonic anhydrases are ubiquitously expressed enzymes that reversibly hydrate carbon dioxide to bicarbonate and protons. While the main function of carbonic anhydrases is to regulate pH and osmotic balance, their involvement in other physiological processes remains to be explored. This study analysed changes in mRNA and protein levels of carbonic anhydrase II in human primary keratinocytes treated with various toll-like receptor agonists and cytokines. A significant upregulation of carbonic anhydrase II at the mRNA and protein levels was observed upon treatment with polyinosinic-polycytidylic acid, a toll-like receptor 3 agonist. Furthermore, in agreement with the increased expression of carbonic anhydrase II in atopic dermatitis skin, carbonic anhydrase II was upregulated by the Th2 cytokines interleukins -4 and -13. In conclusion, these results suggest a potential role of carbonic anhydrase II in Th2-dependent and toll-like receptor 3-induced pathways in inflammatory skin conditions.

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Carbonic anhydrase inhibitory properties of some uracil derivatives

Cited by 38 publications

References 33 publications

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies

Toll-like Receptor 3 Agonist, Polyinosinic-polycytidylic Acid, Upregulates Carbonic Anhydrase II in Human Keratinocytes

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