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

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.