Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action.
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Mincione F, Benedini F, Biondi S, Cecchi A, Temperini C, Formicola G, Pacileo I, Scozzafava A, Masini E, Supuran CT
Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3216-21. doi: 10.1016/j.bmcl.2011.04.046. Epub 2011 Apr 20.
- PubMed ID
- 21549597 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 12 Ki (nM) 5.7 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Acetazolamide Carbonic anhydrase 4 Ki (nM) 74 N/A N/A Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 N/A N/A Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 N/A N/A Details Diclofenamide Carbonic anhydrase 4 Ki (nM) 15000 N/A N/A Details Dorzolamide Carbonic anhydrase 1 Ki (nM) 50000 N/A N/A Details Dorzolamide Carbonic anhydrase 2 Ki (nM) 9 N/A N/A Details Dorzolamide Carbonic anhydrase 4 Ki (nM) 8500 N/A N/A Details