The dual inhibition against the activity and expression of tyrosine phosphatase PRL-3 from a rhodanine derivative

Compound 4 in the six designed rhodanine derivatives strongly inhibited the activity and selectively decreased the expression of PRL-3. The dual inhibition improved the phosphorylation of some PRL-3 substrates and resulted in the decrease of the survival rate of SW-480 cells and apoptosis, indicated that 4 is a promising anti-cancer candidate targeting PRL-3. [Display omitted] •Compound 4 effectively inhibited PRL-3 with IC50 value of 15.22 μM.•Compound 4 selectively inhibited the expression of PRL-3.•Compound 4 increased the phosphorylation of PRL-3 substrates.•Compound 4 decreased the survival rate of SW-480 cells and induce apoptosis. Increasing evidences demonstrated that PRL-3 was associated with metastatic potential in a variety of cancers including CRC, gastric cancer, ovarian cancer and so on. PRL-3 knock down inhibited the development of metastasis by reducing the size of primary tumors and inhibiting the invasion and growth of cancer cells. Therefore, PRL-3 is a promising diagnostic marker and therapeutic target in tumors. So far, only several PRL-3 inhibitors have been reported. In this study, six rhodanine derivatives were synthesized and characterized. The compounds were evaluated against tyrosine phosphatase PRL-3. Among these compounds, 5-(5-chloro-2-(trifluoromethyl)benzylidene)-2-thioxothiazolidin-4-one (4) could effectively inhibit PRL-3 with IC50 value of 15.22 μM. Fluorescent assays suggested compound 4 tightly bound to tyrosine phosphatase PRL-3 with the molar ratio of 1:1, and the binding constant of 1.74 × 106 M−1. Compound 4 entered into SW-480 cells, selectively inhibited the expression of PRL-3 and increased the phosphorylation of PRL-3 substrates, and decreased the survival rate of SW-480 cells with IC50 of 6.64 μM and induced apoptosis. The results revealed that compound 4 is a dual functional inhibitor against the activity and expression of PRL-3 and a promising anti-cancer candidate targeting PRL-3.