Інгібування глутатіон-S-трансфераз калікс[4]аренфосфіновими кислотами
Calix[4]arene-, thiacalix[4]arene- and sulfonylcalix[4]arene-based derivatives with upper rim phosphinic acid groups were studied as inhibitors of glutathione S-transferases. It was found that the macrocyclic compounds can exhibit good to potent activity against GST from equine liver and human recom...
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| Datum: | 2022 |
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| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | English |
| Veröffentlicht: |
V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2022
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| Schlagworte: | |
| Online Zugang: | https://bioorganica.com.ua/index.php/journal/article/view/16 |
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| Назва журналу: | Ukrainica Bioorganica Acta |
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Ukrainica Bioorganica Acta| Zusammenfassung: | Calix[4]arene-, thiacalix[4]arene- and sulfonylcalix[4]arene-based derivatives with upper rim phosphinic acid groups were studied as inhibitors of glutathione S-transferases. It was found that the macrocyclic compounds can exhibit good to potent activity against GST from equine liver and human recombinant GSTA1-1, while being selective over the enzyme from human placenta and GSTP1-1. The thiacalix[4]arene phosphinic acid was the most active inhibitor of equine liver GST and GSTA1-1 with IC50 values of 85 nM and 50 nM, respectively. Kinetic studies revealed that the inhibition was of non-competitive type concerning both enzyme substrates, glutathione, and 1-chloro-2,4-dinitrobenzene. Molecular docking was carried out to predict possible binding sites for thiacalix[4]arene-based phosphinic acid on the surface of homodimeric GSTA1-1. |
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