Carbonic anhydrase activators. Part 17. Synthesis and activation study of a series of 1-1,2,4-triazole-(1H)-3-yl)-2,4,6-trisubstituted-pyridinium salts against isozymes I, II and IV

A series of pyridinium salts were prepared by reaction of 3-amino-(1H)-1,2,4-triazole with 2,4,6-trisubstituted pyrylium salts. The new compounds have been characterized by standard procedures and were assayed for their interaction with three carbonic anhydrase (CA) isozymes, the cytosolic CA I and CA II, as well as the membrane-bound CA IV. The pyridinium salts activate the three isozymes in a different manner, with CA IV being the most susceptible to activation, followed by CA I, whereas CA II is the least sensitive to this class of activators. Compounds possessing 2,6-dialkyl-4-phenyl substituents at the pyridinium ring were the most effective activators. This is the first study of comparative activation for several CA isozymes, proving that activators, similarly to inhibitors possess isozyme-specificity.