Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design.
X-ray crystal structures of the adducts of human carbonic anhydrase (hCA) isozyme II with derivatives incorporating a sulfamide or sulfamic acid moiety are reported. The absence of a C-SO(2)NH(2) bond in the first type of compound can be exploited for the design of more potent and selective CA inhibitors. This study also explains why sulfate is a several-orders-of-magnitude weaker CA inhibitor compared to derivatives incorporating sulfonamide/sulfamide moieties.
Abbate
Francesco
F
Laboratorio di Chimica Inorganica e Bioinorganica, Università degli Studi di Firenze, Via Gino Capponi 7, I-50121, Florence, Italy.
Supuran
Claudiu T
CT
Scozzafava
Andrea
A
Orioli
Pierluigi
P
Stubbs
Milton T
MT
Klebe
Gerhard
G
D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D008024:Ligands; D013449:Sulfonamides; D013451:Sulfonic Acids; C005741:sulfamic acid; D024402:Carbonic Anhydrase II