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Ukr. Bioorg. Acta 2020, Vol. 15, N2, 32-39.

Synthesis and evaluation of new thiazole-containing rhodanine-3-alkanoic acids as inhibitors of protein tyrosine phosphatases and glutathione S-transferases

Oleksandr L. Kobzar, Vitaliy O. Sinenko, Yuriy V. Shulha, Vlasyslav M. Buldenko, Diana M. Hodyna, Stepan G. Pilyo, Volodymyr S. Brovarets and Andriy I. Vovk*

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

Thiazole-containing derivativesof rhodanine-3-alkanoic acids with propanoic or undecanoic acid groups were synthesized and evaluated as inhibitors of some protein tyrosine phosphatases and glutathione S-transferases. The rhodanines bearing longer carboxylated N-alkyl chain were found to inhibit PTP1B, MEG1, MEG2, and VE-PTP as well as GST from equine liver and GSTA1-1 with IC50 values in the low micromolar range. The inhibitory effect on protein tyrosine phosphatase activity depends on substituent at position 2 of the thiazole ring. The best compound showed a competitive type of VE-PTP inhibition. In case of GST from equine liver, the inhibition was of mixed or non-competitive type with respect to glutathione or CDNB substrate, respectively. Possible binding modes of the inhibitors were discussed based on molecular docking calculations.

rhodanine; thiazole; protein tyrosine phosphatase, glutathione S-transferase; enzyme inhibition; molecular docking.

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