Sulfonamide inhibition studies of two β-carbonic anhydrases from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2
| العنوان: | Sulfonamide inhibition studies of two β-carbonic anhydrases from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2 |
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| المؤلفون: | Stefanie Pöggeler, Ronny Lehneck, Daniela Vullo, Claudiu T. Supuran |
| المصدر: | Journal of Enzyme Inhibition and Medicinal Chemistry Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 33, Iss 1, Pp 390-396 (2018) |
| بيانات النشر: | Taylor & Francis, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Short Communication, Hyphae, 01 natural sciences, Sordaria macrospora, 03 medical and health sciences, Structure-Activity Relationship, Dorzolamide, Carbonic anhydrase, Drug Discovery, sulfonamide, medicine, Structure–activity relationship, Methazolamide, Carbonic Anhydrase Inhibitors, Carbonic Anhydrases, Pharmacology, chemistry.chemical_classification, Sulfonamides, biology, Ethoxzolamide, Dose-Response Relationship, Drug, Molecular Structure, Sulfonamide (medicine), lcsh:RM1-950, fungus, General Medicine, biology.organism_classification, 0104 chemical sciences, inhibitor, 010404 medicinal & biomolecular chemistry, 030104 developmental biology, Enzyme, lcsh:Therapeutics. Pharmacology, chemistry, Biochemistry, sulfamate, biology.protein, medicine.drug |
| الوصف: | The two β-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic sulfonamides and one sulfamate, many of which are clinically used agents. CAS1 was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3-chlorosulfanilamide (KIs in the range of 43.2–79.6 nM), whereas acetazolamide, methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were medium potency inhibitors (KIs in the range of 360–445 nM). CAS2 was less sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4-thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4-hydroxymethyl-benzenesulfonamide, with KIs in the range of 48.1–92.5 nM. Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam, celecoxib, and sulthiame were medium potency CAS2 inhibitors (KIs of 143–857 nM). Many other sulfonamides showed affinities in the high micromolar range or were ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor led to important differences of the activity. As these enzymes may show applications for the removal of anthropically generated polluting gases, finding modulators of their activity may be crucial for designing environmental-friendly CO2 capture processes. |
| اللغة: | English |
| تدمد: | 1475-6374 1475-6366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::236ca8886767599512bfbfe2aa48724cTest http://europepmc.org/articles/PMC6010127Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....236ca8886767599512bfbfe2aa48724c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14756374 14756366 |
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