A dioxidovanadium (V) complex of NNO-donor Schiff base as a selective inhibitor of protein tyrosine phosphatase 1B: Synthesis, characterization, and biological activities.

A new dioxidovanadium (V) complex, VO2(HPPCH) (1) (H2PPCH = N'-picolinoylpyridin-1-ium-2-carbohydrazonate) has been synthesized and characterized by elemental analysis, IR, X-ray diffraction analysis and electrospray ionization mass spectra. Complex 1 crystallized in the monoclinic system with space group P21/c. It potently inhibited PTP1B with IC50 of 0.13 μM, about 7, 15 and 125-fold stronger against PTP1B than over TCPTP, SHP-1 and SHP-2, displaying obvious selectivity against PTP1B. Western blotting analysis indicated that complex 1 effectively increased the phosphorylation of PTP1B substrates, especially the phosphorylation of IR/IGF 1R and IRS-1. It exhibited lower cytotoxicity than positive control VOSO4. These results make complex 1 a promising candidate for novel anti-diabetic drug development.