%0 Journal Article
%T ¦Á,¦Ã-Diketocarboxylic Acids and Their Esters Act as Carbonic Anhydrase IX and XII Selective Inhibitors
%J -
%D 2019
%R https://doi.org/10.1021/acsmedchemlett.9b00023
%X Among human carbonic anhydrase (CA) inhibitors, the ¦Á,¦Ã-diketocarboxylic acids and esters are still poorly investigated. Here, we report the first compounds of this class (1¨C6) acting as potent inhibitors at low nanomolar level against the cancer-related human CA IX and XII, and 2¨C3 magnitude orders selective toward the cytosolic isoforms hCA I and II. At enzymatic level, the ¦Á,¦Ã-diketoacids 1¨C3 were more effective inhibitors compared to the corresponding ethyl esters 4¨C6. The phenyl- and ¦Á-naphthyl-containing compounds (1, 3, 4, and 6) behaved as dual hCA IX/XII inhibitors, while the ¦Â-naphthyl analogues (2 and 5) exhibited hCA IX-selective inhibition. In MG63 and HOS osteosarcoma (OS) cell lines, the ethyl esters 5 and 6 displayed dose-dependent reduction of viability and proliferation after 72 h treatment, with 6 being more potent than 5 likely for its dual hCA IX/XII inhibition
%U https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00023