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Ukr. Bioorg. Acta 2021, Vol. 16, N2, 12-22.

DOI: https://doi.org/10.15407/bioorganica2021.02.012

Nitro-substituted aurones as xanthine oxidase inhibitors

Oleksandr L. Kobzar1, Iryna M. Mischenko1, Alona V. Tatarchuk1, Vasyl S. Vdovin2, Sergiy S. Lukashov2, Sergiy M. Yarmoluk2 and Andriy I. Vovk1*

1 V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine,
1 Murmanska St., Kyiv, 02094, Ukraine

tel.: +380-44-558-5388; e-mail: vovk@bpci.kiev.ua
2 Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, 150 Zabolotnogo St., 03143 Kyiv, Ukraine

Aurone derivatives possessing a wide range of biological activities are of high interest in medicinal chemistry. Carboxylated aurones were found previously to inhibit xanthine oxidase, which is a potential target for treatment of hyperuricemia and gout. In this paper, a series of B-ring nitro-substituted aurone derivatives were studied in vitro as inhibitors of this enzyme. The introduction of hydroxyl group into the B-ring of nitro-functionalized aurones resulted in significant increase of their inhibitory potency. At the same time, aurones chlorinated at ring A and containing nitro and hydroxyl groups at ring B showed only slightly increased inhibition effect. The kinetic studies and molecular docking calculations were carried out to explain the inhibition mechanism of xanthine oxidase by the nitro-substituted aurone derivatives.

aurone; xanthine oxidase; inhibition; kinetics; molecular docking.

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