AI Article Synopsis
- Three series of polcyclic compounds with primary sulfonamide or carboxylic acid groups were studied for their ability to inhibit four types of carbonic anhydrase (CA) enzymes: hCA I, II, IX, and XII.
- Most of the new sulfonamides showed strong inhibition against hCA II, IX, and XII, but did not selectively inhibit any single isoform.
- In contrast, the carboxylate compounds were able to selectively inhibit hCA IX with inhibition constants between 40.8 and 92.7 nM, while having minimal effects on the other isoforms, suggesting potential for designing targeted carbonic anhydrase inhibitors (CAIs).
Article Abstract
Three series of polycyclic compounds possessing either primary sulfonamide or carboxylic acid moieties as zinc-binding groups were investigated as inhibitors of four physiologically relevant CA isoforms, the cytosolic hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides reported here showed excellent inhibitory effects against isoforms hCA II, IX and XII, but no highly isoform-selective inhibition profiles. On the other hand, the carboxylates selectively inhibited hCA IX (KIs ranging between 40.8 and 92.7nM) without inhibiting significantly the other isoforms. Sulfonamides/carboxylates incorporating polycyclic ring systems such as benzothiopyranopyrimidine, pyridothiopyranopyrimidine or dihydrobenzothiopyrano[4,3-c]pyrazole may be considered as interesting candidates for exploring the design of isoform-selective CAIs with various pharmacologic applications.
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| http://dx.doi.org/10.1016/j.bmc.2016.01.018 | DOI Listing |
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