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

Thiazole-containing derivatives of 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.