Synthesis and evaluation of copper complexes of Schiff-base condensates from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as selective inhibitors of protein tyrosine phosphatases

Five copper complexes, [Cu(bhbb,chbb,ohbb)(H2O)(n)] (tridentate-ligands: H(2)bhbb = 2-(5-bromo-2-hydroxylbenzylideneamino)benzoic acid, 1; H(2)chbb = 2-(5-chloro-2-hydroxylbenzylideneamino)benzoic acid, 2; H(2)nhbb = 2-(5-nitro-2-hydroxyl-benzylideneamino)benzoic acid, 3) and [Cu(cpmp,npmp)(2)] (bidentate-ligands: Hcpmp = 4-chloro-2-((phenylimino)methyl)phenol, 4; Hnpmp = 4-bromo-2-((phenyl-imino)methyl)phenol, 5) have been prepared and characterized by EA, IR, EPR UV-Vis, and ESI-MS. Structure-activity relationship of copper complexes in inhibiting protein tyrosine phosphatases (protein tyrosine phosphatase 1B, PTP1B; T-cell protein tyrosine phosphatase, TCPTP; megakaryocyte protein-tyrosine phosphatase, PTP-MEG2; Src homology phosphatase 1, SHP-1 and Src homology phosphatase 2, SHP-2) is investigated. Inhibitory activities of complexes against the five PTPs indicate that they potently inhibit PTP1B, TCPTP, PTP-MEG2 and SHP-1, but do not inhibit SHP-2. In the complexes, 5 exhibits very strong inhibition (IC50, 0.059 mu M) and better selectivity against PTP1B while 1 and 2 show very strong inhibition (IC50 = 0.089 and 0.067 mu M) and a little selectivity against TCPTP. Compared with the oxovanadium(IV) complexes of same ligands, the copper complexes increase the inhibitory ability against TCPTP, PTP-MEG2 and SHP-1 but decrease the inhibition against SHP-2. For complex 5, the inhibition over PTP1B, TCPTP, PTP-MEG2 and SHP-1 are all improved about 5- to 15-fold compared with the oxovanadium(IV) complex. The results demonstrate that both the ligand structures and the center metals influence the inhibition and selectivity against different PTPs. (C) 2013 Elsevier B.V. All rights reserved.