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Carboxylated chalcones and related flavonoids as inhibitors of xanthine oxidase

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Abstract

Carboxylated chalcones and other related flavonoids were synthesized and evaluated as inhibitors of xanthine oxidase, which is a known target for synthetic and herbal drugs used against hyperuricemia, gout, and other diseases. The 4-carboxylated chalcones with hydroxy, methoxy, and ethoxy groups at ring A were found to exhibit in vitro inhibitory activities with IC50 values in the range of 0.057 to 0.26 μM, being 10–60-fold more potent than allopurinol. Structurally related carboxylic acids with Δ3,9-homoisoflavonoid and flavone scaffolds also showed micromolar activity towards xanthine oxidase. At the same time, dihydrochalcone and Δ2,3-homoisoflavonoid carboxylic acids as well as their oxa-analogues were more than two orders of magnitude less effective inhibitors. Kinetic and molecular docking studies indicated that the carboxylated chalcones and Δ3,9-homoisoflavonoids are mixed-type inhibitors, which mostly bind to free enzyme occupying the active site of xanthine oxidase.

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Acknowledgements

This work was supported by the National Academy of Sciences of Ukraine.

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Authors and Affiliations

  1. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, Ukraine

    Oleksandr L. Kobzar, Alona V. Tatarchuk, Galyna P. Mrug, Bohdan A. Demydchuk, Mykhaylo S. Frasinyuk & Andriy I. Vovk

  2. Department of Food Chemistry, National University of Food Technologies, Kyiv, 01601, Ukraine

    Svitlana P. Bondarenko

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Kobzar, O.L., Tatarchuk, A.V., Mrug, G.P. et al. Carboxylated chalcones and related flavonoids as inhibitors of xanthine oxidase. Med Chem Res 32, 1804–1815 (2023). https://doi.org/10.1007/s00044-023-03109-8

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