Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action
| Autor: | Claudiu T. Supuran, Francesca Benedini, Francesco Mincione, Alessandro Cecchi, Claudia Temperini, Ilaria Pacileo, Giuseppe Formicola, Andrea Scozzafava, Emanuela Masini, Stefano Biondi |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular genetic structures Stereochemistry Clinical Biochemistry Pharmaceutical Science Ocular hypertension Thiophenes Crystallography X-Ray Nitric Oxide Biochemistry Chemical synthesis Dorzolamide Carbonic anhydrase Drug Discovery medicine Animals Humans Protein Isoforms Carbonic Anhydrase Inhibitors Molecular Biology chemistry.chemical_classification Sulfonamides Molecular Structure biology Chemistry Organic Chemistry Glaucoma medicine.disease eye diseases In vitro Sulfonamide Disease Models Animal Enzyme Enzyme inhibitor biology.protein Molecular Medicine Ocular Hypertension Rabbits medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:3216-3221 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2011.04.046 |
| Popis: | Several aromatic/heterocyclic sulfonamide scaffolds have been used to synthesize compounds incorporating NO-donating moieties of the nitrate ester type, which have been investigated for the inhibition of five physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms: hCA I (offtarget), II, IV and XII (antiglaucoma targets) and IX (antitumor target). Some of the new compounds showed effective in vitro inhibition of the target isoforms involved in glaucoma, and the X-ray crystal structure of one of them revealed factors associated with the marked inhibitory activity. In an animal model of ocular hypertension, one of the new compounds was twice more effective than dorzolamide in reducing elevated intraocular pressure characteristic of this disease, anticipating their potential for the treatment of glaucoma. |
| Databáze: | OpenAIRE |
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