title: Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases.
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.
authors.affiliation: 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.
authors.forename: Liping
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.forename: Miaoli
authors.initials: M
authors.lastname: Zhu
authors.forename: Sulian
authors.initials: S
authors.lastname: Wang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Shu
authors.initials: S
authors.lastname: Xing
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
mesh_terms: D001645:Biguanides / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D014638:Vanadates / Q000737:chemistry*
chemical_list: D001645:Biguanides; D004791:Enzyme Inhibitors; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases