Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides

0365071 - ÚMG 2012 RIV US eng J - Journal Article
Mader, Pavel - Brynda, Jiří - Gitto, R. - Agnello, S. - Pachl, Petr - Supuran, C. T. - Chimirri, A. - Řezáčová, Pavlína
Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides.
Journal of Medicinal Chemistry. Roč. 54, č. 7 (2011), s. 2522-2526. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR GA203/09/0820
Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z40550506
Keywords : carbonic anhydrase * isoquinolinesulfonamides * selective inhibition * crystal structure
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.248, year: 2011

lsoquinolinesulfonamides inhibit human carbonic anhydrases (hCAs) and display selectivity toward therapeutically relevant isozymes. The crystal structure of hCA 11 in complex with 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamide revealed unusual inhibitor binding. Structural analyses allowed for discerning the fine details of the inhibitor binding mode to the active site, thus providing clues for the future design of even more selective inhibitors for druggable isoforms such as the cancer associated hCA IX and neuronal hCA VII.
Permanent Link: http://hdl.handle.net/11104/0200407