Inhibition of glutathione S-transferases by calix[4]arene-based phosphinic acids

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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Published in:Ukrainica bioorganica acta : UBA 2022-06, Vol.17 (1), p.86-91
Main Authors: Kobzar, Oleksandr, Shulha, Yuriy, Buldenko, Vladyslav, Drapailo, Andriy, Kalchenko, Vitaly, Vovk, Andriy
Format: Article
Language:English
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Summary: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
ISSN:1814-9758
1814-9766
DOI:10.15407/bioorganica2022.01.086