Synthesis, characterization, and protein tyrosine phosphatases inhibition activities of oxovanadium(IV) complexes with Schiff base and polypyridyl derivatives |
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Authors: | Caixia Yuan Yanbo Wu Maolin Guo Shu Xing Miaoli Zhu |
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Affiliation: | a Institute of Molecular Science, the Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan, 030006, China b Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, Dartmouth, MA 02747, USA c Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun 130023, China |
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Abstract: | Seven new mixed-ligand vanadyl complexes, [VIVO(5-Br-SAA)(NN)] and [VIVO(2-OH-NAA)(NN)] (1-7) (5-Br-SAA for 5-bromosalicylidene anthranilic acid, 2-OH-NAA for 2-hydroxy-1-naphthaldehyde anthranilic acid and NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1 and 5), 1,10-phenanthroline (phen, 2 and 6), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3 and 7), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), were synthesized and characterized. X-ray crystal structure of [VIVO(5-Br-SAA)(phen)] revealed a distorted octahedral geometry with the Schiff base ligand coordinated in a tridentate ONO-fashion and the phenanthroline ligand in a bidentate fashion. Density-functional theory (DFT) calculations suggest a similar structure and the same coordination mode for all the other oxovanadium complexes synthesized. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), with IC50 values approximately 41-75 nM. Kinetics assays suggest that the complexes inhibit PTP1B in a competitive manner. Notably, they had moderate selectivity of PTP1B over T-cell protein tyrosine phosphatase (TCPTP) (about 2-fold) and good selectivity over Src homology phosphatase 1 (SHP-1) (about 4∼7-fold). Thus, these mixed-ligand complexes represent a promising class of PTP1B inhibitors for future development as anti-diabetic agents. |
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Keywords: | Oxovanadium(IV) complexes Protein tyrosine phosphatase 1B T-cell protein tyrosine phosphatase Src homology phosphatase 1, inhibitor |
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