Carbonic anhydrase inhibitors: Selective inhibition of the extracellular, tumor-associated isoforms IX and XII over isozymes I and II with glycosyl-thioureido-sulfonamides.
A series of glycosyl-thioureido sulfonamides incorporating glucosamine, galactosamine, and mannosamine tails, and sulfanilamide, halogenosulfanilamide, and metanilamide heads was synthesized. Many of the new compounds showed micromolar-submicromolar affinity for the inhibition of the cytosolic isoforms I and II of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), but low nanomolar binding to the tumor-associated isozymes, CA IX and XII. The selectivity ratios for the inhibition of the tumor-associated over the cytosolic isozymes were in the range of 107-955 for the most selective such inhibitors.
Smaine
Fatma-Zohra
FZ
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Winum
Jean-Yves
JY
Montero
Jean-Louis
JL
Regainia
Zine
Z
Vullo
Daniela
D
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides