5E2S

Crystal structure of human carbonic anhydrase II in complex with the 4-(2-iso-propylphenyl)benzenesulfonamide inhibitor

Summary for 5E2S

• Entry DOI: 10.2210/pdb5e2s/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 2'-(propan-2-yl)biphenyl-4-sulfonamide, ... (4 entities in total)
• Functional Keywords: lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29411.56

Authors

Ferraroni, M.,Supuran, C.T. (deposition date: 2015-10-01, release date: 2016-01-20, Last modification date: 2024-01-10)

Primary citation

Cornelio, B.,Laronze-Cochard, M.,Ceruso, M.,Ferraroni, M.,Rance, G.A.,Carta, F.,Khlobystov, A.N.,Fontana, A.,Supuran, C.T.,Sapi, J.
4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies.
J.Med.Chem., 59:721-732, 2016

PubMed Abstract: Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.

PubMed: 26741028
DOI: 10.1021/acs.jmedchem.5b01771

Experimental method

X-RAY DIFFRACTION (1.5 Å)