Investigation of carbonic anhydrase inhibitory potency of (Z/E)-alkyl N'-benzyl-N-(arylsulfonyl)-carbamimidothioates.

Aim: Among 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, two (hCA IX and XII) play important roles in the growth and survival of tumor cells, making them therapeutic targets for cancer treatment. This study aimed to develop novel sulfonamide-based compounds as selective hCA IX and XII inhibitors. Materials & methods: A library of novel N-sulfonyl carbamimidothioates was obtained for CA inhibitory activity studies against four hCA isoforms. Results: None of the developed compounds displayed inhibitory potential against off-target isoforms hCA I and II. However, they effectively inhibited tumor-associated hCA IX and XII. Conclusion: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity.

An α-carbonic anhydrase from the thermophilic bacterium Sulphurihydrogenibium azorense is the fastest enzyme known for the CO2 hydration reaction.

We report the biochemical characterization of a new carbonic anhydrase (CA, EC 4.2.1.1), named SazCA, identified by translated genome inspection in Sulfurihydrogenibium azorense, a thermophilic bacterium from terrestrial hot springs of the Azores. SazCA is an α-CA showing kinetic parameters that make it the fastest enzyme of the CA family described so far. The biochemical properties, thermostability and inhibition of SazCA were compared with those of the thermophilic and mesophilic counterparts, demonstrating the special features of this unique enzyme.

The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.

The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was investigated for its inhibition with a large series of sulfonamides and a sulfamate, the classical inhibitors of these zinc enzymes. SspCA showed an inhibition profile with these compounds very similar to that of the predominant human cytosolic isoform hCA II, and not to that of the bacterial α-CA from Helicobacter pylori. Some clinically used drugs such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulthiame were low nanomolar SspCA/hCA II inhibitors (KIs in the range of 4.5-12.3nM) whereas simple aromatic/heterocyclic sulfonamides were less effective, micromolar inhibitors. As this highly catalytically active and thermostable enzyme may show biotechnological applications, its inhibition studies may be relevant for designing on/off systems to control its activity.