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

Yuqi Jia; Liping Lu; Miaoli Zhu; Caixia Yuan; Shu Xing; Xueqi Fu

doi:10.1016/j.ejmech.2017.02.003

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

Eur J Med Chem. 2017 Mar 10:128:287-292. doi: 10.1016/j.ejmech.2017.02.003. Epub 2017 Feb 6.

Authors

Yuqi Jia¹, Liping Lu², Miaoli Zhu³, Caixia Yuan¹, Shu Xing⁴, Xueqi Fu⁵

Affiliations

¹ Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, People's Republic of China.
² Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, People's Republic of China. Electronic address: luliping@sxu.edu.cn.
³ Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, People's Republic of China. Electronic address: miaoli@sxu.edu.cn.
⁴ Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China. Electronic address: xingshu@jlu.edu.cn.
⁵ Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.

PMID: 28199951
DOI: 10.1016/j.ejmech.2017.02.003

Abstract

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.

Keywords: Cytotoxicity; Dioxidovanadium (V) complex; Inhibitor; Protein tyrosine phosphatase 1B; Selectivity.

MeSH terms

Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects*
Crystallography, X-Ray
Hep G2 Cells
Humans
Models, Molecular
Molecular Structure
Organometallic Compounds / chemical synthesis*
Organometallic Compounds / pharmacology*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Schiff Bases / chemistry*
Vanadates / chemistry*

Substances

Antineoplastic Agents
Organometallic Compounds
Schiff Bases
Vanadates
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1