Isoquinolinesulfonamides inhibit human carbonic anhydrases (hCAs) and display selectivity toward therapeutically relevant isozymes. The crystal structure of hCA II 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.
Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides / P. Mader;J. Brynda;R. Gitto;S. Agnello;P. Pachl;C. T. Supuran;A. Chimirri;P. Řezáčová. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 54:(2011), pp. 2522-2526.
Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides.
SUPURAN, CLAUDIU TRANDAFIR;
2011
Abstract
Isoquinolinesulfonamides inhibit human carbonic anhydrases (hCAs) and display selectivity toward therapeutically relevant isozymes. The crystal structure of hCA II 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.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.