ArticleFuture medicinal chemistry2026
Novel isocoumarin-pyrazole hybrids: synthesis, characterization, and investigation of their carbonic anhydrase inhibitory activities.
Article in Future medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimSelective inhibition of tumor-associated carbonic anhydrase (CA) isoforms IX and XII is a key challenge in anticancer drug discovery, as most inhibitors cause off-target inhibition of cytosolic enzymes. We addressed this by designing and synthesizing a series of isocoumarin - pyrazole hybrids from isocoumarin - chalcone scaffolds and evaluating their potential as selective CA IX/XII inhibitors. MATERIALS AND
methodsHybrids (
resultsAll compounds were obtained in good yields. No significant activity was observed against cytosolic hCA I and II, whereas all derivatives inhibited tumor-associated hCA IX and XII at low-to-medium micromolar levels. Electron-donating substituents improved potency, with compounds
conclusionThis study shows that isocoumarin - pyrazole hybrids achieve selective inhibition of hCA IX and XII without affecting off-target isoforms. The results expand the chemical space of non-classical CA inhibitors and offer insights for the rational design of selective anticancer agents. Future work will focus on optimizing potency and evaluating efficacy in cellular tumor models.
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