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.