Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases

Liping Lu; Xiaoli Gao; Miaoli Zhu; Sulian Wang; Qiong Wu; Shu Xing; Xueqi Fu; Zhiwei Liu; Maolin Guo

doi:10.1007/s10534-012-9548-4

Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases

Biometals. 2012 Jun;25(3):599-610. doi: 10.1007/s10534-012-9548-4. Epub 2012 May 1.

Authors

Liping Lu¹, Xiaoli Gao, Miaoli Zhu, Sulian Wang, Qiong Wu, Shu Xing, Xueqi Fu, Zhiwei Liu, Maolin Guo

Affiliation

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.

PMID: 22547055
DOI: 10.1007/s10534-012-9548-4

Abstract

The inhibitory effects of three biguanido-oxovanadium complexes ([VO(L(1-3))(2)]·nH(2)O: HL(1) = metformin, HL(2) = phenformin, HL(3) = moroxydine) against four protein tyrosine phosphatases (PTPs) and an alkaline phosphatase (ALP) were investigated. The complexes display strong inhibition against PTP1B and TCPTP (IC(50), 80-160 nM), a bit weaker inhibition against HePTP (IC(50), 190-410 nM) and SHP-1(IC(50), 0.8-3.3 μM) and much weaker inhibition against ALP (IC(50), 17-35 μM). Complex 3 is about twofold less potent against PTP1B, TCPTP and HePTP than complexes 1 and 2, while complex 2 inhibits SHP-1 more strongly (about three to fourfold) than the other two complexes. These results suggest that the structures of the ligands slightly influence the potency and selectivity against PTPs. The complexes inhibit PTP1B and ALP with a typical competitive type.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biguanides / chemistry*
Enzyme Activation / drug effects
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Protein Tyrosine Phosphatases / metabolism*
Vanadates / chemistry*

Substances

Biguanides
Enzyme Inhibitors
Vanadates
Protein Tyrosine Phosphatases