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- W2916876648 abstract "Among human carbonic anhydrase (CA) inhibitors, the α,γ-diketocarboxylic acids and esters are still poorly investigated. Here, we report the first compounds of this class (1–6) acting as potent inhibitors at low nanomolar level against the cancer-related human CA IX and XII, and 2–3 magnitude orders selective toward the cytosolic isoforms hCA I and II. At enzymatic level, the α,γ-diketoacids 1–3 were more effective inhibitors compared to the corresponding ethyl esters 4–6. The phenyl- and α-naphthyl-containing compounds (1, 3, 4, and 6) behaved as dual hCA IX/XII inhibitors, while the β-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." @default.
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- W2916876648 date "2019-02-19" @default.
- W2916876648 modified "2023-10-18" @default.
- W2916876648 title "α,γ-Diketocarboxylic Acids and Their Esters Act as Carbonic Anhydrase IX and XII Selective Inhibitors" @default.
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- W2916876648 doi "https://doi.org/10.1021/acsmedchemlett.9b00023" @default.
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