3NI5

Carbonic anhydrase inhibitor: C1 family

Summary for 3NI5

• Entry DOI: 10.2210/pdb3ni5/pdb
• Related: 3NJ9
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, inhibitors, sulfonamide, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 30036.54

Authors

Temperini, C.,Cecchi, A.,Scozzafava, A.,Supuran, C.T. (deposition date: 2010-06-15, release date: 2011-06-22, Last modification date: 2023-11-01)

Primary citation

Mincione, F.,Benedini, F.,Biondi, S.,Cecchi, A.,Temperini, C.,Formicola, G.,Pacileo, I.,Scozzafava, A.,Masini, E.,Supuran, C.T.
Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action
Bioorg.Med.Chem.Lett., 21:3216-3221, 2011

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.

PubMed: 21549597
DOI: 10.1016/j.bmcl.2011.04.046

Experimental method

X-RAY DIFFRACTION (2.1 Å)