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Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities

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Abstract

A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic acid (SAA)], and a bidentate NN ligand [viz., 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[3,2-a:2′,3′-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2′,3′-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry, UV–vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of both complexes, [VIVO(SAA)(bpy)]·0.25bpy and [VIVO(SAA)(phen)]·0.33H2O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO3N3). The oxidation state of V(IV) with d 1 configuration was confirmed by EPR spectroscopy. The speciation of VO–SAA–bpy in aqueous solution was investigated by potentiomtreic pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0–7.4, and one is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine phosphatase 1B (PTP1B) (IC50 approximately 30–61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [VIVO(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents.

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Abbreviations

BMOV:

Bis(maltolato)oxovanadium

bpy:

2,2′-Bipyridine

dppm:

7-Methyldipyrido[3,2-a:2′,3′-c]phenazine

DFT:

Density functional theory

DMSO:

Dimethyl sulfoxide

dppz:

Dipyrido[3,2-a:2′,3′-c]phenazine

dpq:

Dipyrido[3,2-d:2′,3′-f]quinoxaline

ESI-MS:

Electrospray ionization mass spectrometry

IPTG:

Isopropyl β-d-thiogalactopyranoside

LB:

Luria–Bertani

2-ME:

2-Mercaptoethanol

MOPS:

3-Morpholinopropanesulfonic acid

pNPP:

p-Nitrophenol phosphate

phen:

1,10-Phenanthroline

PTP:

Protein tyrosine phosphatase

PTP1B:

Protein tyrosine phosphatase 1B

SAA:

Salicylidene anthranilic acid

SHP-1:

Src homology phosphatase 1

TCPTP:

T-cell protein tyrosine phosphatase

Tris:

Tris(hydroxymethyl)aminomethane

References

  1. Zhang S, Zhang ZY (2007) Drug Discov Today 12:373–381

    Article  PubMed  CAS  Google Scholar 

  2. Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A, Godzik A, Hunter T, Dixon J, Mustelin T (2004) Cell 117:699–711

    Article  PubMed  CAS  Google Scholar 

  3. Zhang ZY (2001) Curr Opin Chem Biol 5:416–423

    Article  PubMed  CAS  Google Scholar 

  4. Andersen JN, Jansen PG, Echwald SM, Mortensen OH, Fukada T, Del Vecchio R, Tonks NK, Moller NPH (2004) FASEB J 18:8–30

    Article  PubMed  CAS  Google Scholar 

  5. Arena S, Benvenuti S, Bardelli A (2005) Cell Mol Life Sci 62:2092–2099

    Article  PubMed  CAS  Google Scholar 

  6. Combs AP, Yue EW, Bower M, Ala PJ, Wayland B, Douty B, Takvorian A, Polam P, Wasserman Z, Zhu WY, Crawley ML, Pruitt J, Sparks R, Glass B, Modi D, McLaughlin E, Bostrom L, Li M, Galya L, Blom K, Hillman M, Gonneville L, Reid BG, Wei M, Becker-Pasha M, Klabe R, Huber R, Li YL, Hollis G, Burn TC, Wynn R, Liu P, Metcalf B (2005) J Med Chem 48:6544–6548

    Article  PubMed  CAS  Google Scholar 

  7. Dewang PM, Hsu NM, Peng SZ, Li WR (2005) Curr Med Chem 12:1–22

    PubMed  CAS  Google Scholar 

  8. Zhang ZY, Lee SY (2003) Expert Opin Investig Drug 12:223–233

    Article  CAS  Google Scholar 

  9. Goldstein BJ (2001) Curr Drug Targets Immune Endocr Metabol Disord 1:175–265

    Article  Google Scholar 

  10. Seale AP, de Jesus LA, Kim SY, Choi YH, Lim HB, Hwang CS, Kim YS (2005) Biotechnol Lett 27:221–225

    Article  PubMed  CAS  Google Scholar 

  11. Xie LP, Lee SY, Andersen JN, Waters S, Shen K, Guo XL, Moller NPH, Olefsky JM, Lawrence DS, Zhang ZY (2003) Biochemistry 42:12792–12804

    Article  PubMed  CAS  Google Scholar 

  12. Yuen VG, Caravan P, Gelmini L, Glover N, McNeill JH, Setyawati IA, Zhou Y, Orvig C (1997) J Inorg Biochem 68:109–116

    Article  PubMed  CAS  Google Scholar 

  13. Shrestha S, Bhattarai BR, Lee KH, Cho H (2007) Bioorg Med Chem 15:6535–6548

    Article  PubMed  CAS  Google Scholar 

  14. Sparks RB, Polam P, Zhu W, Crawley ML, Takvorian A, McLaughlin E, Wei M, Ala PJ, Gonneville L, Taylor N, Li Y, Wynn R, Burn TC, Liu PCC, Combs AP (2007) Bioorg Med Chem Lett 17:736–740

    Article  PubMed  CAS  Google Scholar 

  15. Maccari R, Paoli P, Ottana R, Jacomelli M, Ciurleo R, Manao G, Steindl T, Langer T, Vigorita MG, Camici G (2007) Bioorg Med Chem 15:5137–5149

    Article  PubMed  CAS  Google Scholar 

  16. Winter CL, Lange JS, Davis MG, Gerwe GS, Downs TR, Peters KG, Kasibhatla B (2005) Exp Biol Med 230:207–216

    CAS  Google Scholar 

  17. Crans DC, Smee JJ, Gaidamauskas E, Yang LQ (2004) Chem Rev 104:849–902

    Article  PubMed  CAS  Google Scholar 

  18. Rehder D (2003) Inorg Chem Commun 6:604–617

    Article  CAS  Google Scholar 

  19. Shechter Y, Goldwaser I, Mironchik M, Fridkin M, Gefel D (2003) Coord Chem Rev 237:3–11

    Article  CAS  Google Scholar 

  20. Li M, Ding WJ, Baruah B, Crans DC (2008) J Inorg Biochem 102:1846–1853

    Article  PubMed  CAS  Google Scholar 

  21. Thompson KH, Orvig C (2006) J Inorg Biochem 100:1925–1935

    Article  PubMed  CAS  Google Scholar 

  22. Noblia P, Baran EJ, Otero L, Draper P, Cerecetto H, Gonzalez M, Piro OE, Castellano EE, Inohara T, Adachi Y, Sakurai H, Gambino D (2004) Eur J Inorg Chem 322–328

  23. Crans DC, Smee JJ (2004) Comp Coord Chem II 4:175–239

    Article  CAS  Google Scholar 

  24. Ghosh T, Bhattacharya S, Das A, Mukherjee G, Drew MGB (2005) Inorg Chim Acta 358:989–996

    Article  CAS  Google Scholar 

  25. Thompson KH, Orvig C (2000) Dalton Trans 2885–2892

  26. Mukherjee R, Donnay E.G, Radomski MA, Miller C, Redfern DA, Gericke A, Damron DS, Brasch NE (2008) Chem Commun 3783–3785

  27. Peters KG, Davis MG, Howard BW, Pokross M, Rastogi V, Diven C, Greis KD, Eby-Wilkens E, Maier M, Evdokimov A, Soper S, Genbauffe F (2003) J Inorg Biochem 96:321–330

    Article  PubMed  CAS  Google Scholar 

  28. Huyer G, Liu S, Kelly J, Moffat J, Payette P, Kennedy B, Tsaprailis G, Gresser MJ, Ramachandran C (1997) J Biol Chem 272:843–851

    Article  PubMed  CAS  Google Scholar 

  29. Nxumalo F, Glover NR, Tracey AS (1998) J Biol Inorg Chem 3:534–542

    Article  CAS  Google Scholar 

  30. Lu LP, Zhu ML, Guo ML (unpublished work)

  31. Patel RN, Singh N, Gundla VLN (2006) Polyhedron 25:3312–3318

    Article  CAS  Google Scholar 

  32. Dickeson JE, Summers LA (1970) Aus J Chem 23:1023–1027

    CAS  Google Scholar 

  33. Amouyal E, Homsi A, Chambron JC, Sauvage JP (1990) J Chem Soc Dalton Trans 1841–1845

  34. Clague MJ, Keder NL, Butler A (1993) Inorg Chem 32:4757–4761

    Article  Google Scholar 

  35. Gans P, Sabatini A, Vacca A (1985) J Chem Soc Dalton Trans 1195–1200

  36. Moghimi A, Alizadeh R, Shokrollahi A, Aghabozorg H, Shamsipur M, Shockravi A (2003) Inorg Chem 42:1616–1624

    Article  PubMed  CAS  Google Scholar 

  37. Martell AE, Chaberek S Jr, Courtney RC, Westerback S, Hyytiainen H (1957) J Am Chem Soc 79:3036–3041

    Article  CAS  Google Scholar 

  38. Henry RP, Mitchell PCH, Prue JE (1973) J Chem Soc Dalton Trans 1156–1159

  39. Davis CW (1938) J Chem Soc 2093–2098

  40. Chruscinska EL, Sanna D, Garribba E, Micera G (2008) Dalton Trans 4903–4916

  41. Sheldrick GM (1996) Correction software. University of Göttingen, Göttingen

    Google Scholar 

  42. Sheldrick GM (1997) Program for the solution of crystal structure. University of Göttingen, Göttingen

    Google Scholar 

  43. Sheldrick GM (1997) Program for the refinement of crystal structure. University of Göttingen, Göttingen

    Google Scholar 

  44. Sheldrick GM (1999) SHELXTL/PC, version 5.1. Bruker AXS, Madison

    Google Scholar 

  45. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven JT, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03, revision E.01. Gaussian, Wallingford

    Google Scholar 

  46. Hay PJ, Wadt WR (1985) J Chem Phys 82:270–283

    Article  CAS  Google Scholar 

  47. Hay PJ, Wadt WR (1985) J Chem Phys 82:284–298

    Article  Google Scholar 

  48. Hay PJ, Wadt WR (1985) J Chem Phys 82:299–310

    Article  CAS  Google Scholar 

  49. Tong Y, Guo ML (2007) J Biol Inorg Chem 12:735–750

    Article  PubMed  CAS  Google Scholar 

  50. Zhu ZC, Sun M, Zhang XY, Liu KX, Shi DL, Li JD, Su JQ, Xu YC, Fu XQ (2007) Chem Res Chin Univ 23:289–296

    Article  CAS  Google Scholar 

  51. Li WN, Zhuang Y, Li H, Sun Y, Fu Y, Wu XX, Zhao ZZ, Fu X (2008) Chem Res Chin Univ 24:592–596

    Article  CAS  Google Scholar 

  52. Montalibet J, Skorey KI, Kennedy BP (2005) Methods 35:2–8

    Article  PubMed  CAS  Google Scholar 

  53. Ember B, Kamenecka T, LoGrasso P (2008) Biochemistry 47:3076–3084

    Article  PubMed  CAS  Google Scholar 

  54. Mondal S, Rath SP, Rajak KK, Chakravorty A (1998) Inorg Chem 37:1713–1719

    Article  CAS  Google Scholar 

  55. Maurya MR, Kumar A, Ebel M, Rehder D (2006) Inorg Chem 45:5924–5937

    Article  PubMed  CAS  Google Scholar 

  56. Root CA, Hoeschele JD, Cornman CR, Kampf JW, Pecoraro VL (1993) Inorg Chem 32:3855–3861

    Article  CAS  Google Scholar 

  57. Amin SS, Cryer K, Zhang B, Dutta SK, Eaton SS, Anderson OP, Miller SM, Reul BA, Brichard SM, Crans DC (2000) Inorg Chem 39:406–416

    Article  PubMed  CAS  Google Scholar 

  58. Sasmal PK, Patra AK, Nethaji M, Chakravarty AR (2007) Inorg Chem 46:11112–11121

    Article  PubMed  CAS  Google Scholar 

  59. Zamian JR, Dockal ER, Castellano G, Oliva G (1995) Polyhedron 14:2411–2418

    Article  CAS  Google Scholar 

  60. Marques APD, Dockal ER, Skrobot FC, Rosa ILV (2007) Inorg Chem Commun 10:255–261

    Article  CAS  Google Scholar 

  61. Westland AD, Tarafder MTH (1981) Inorg Chem 20:3992–3995

    Article  CAS  Google Scholar 

  62. Bhattacharya S, Ghosh T (2002) Transit Metal Chem 27:89–94

    Article  CAS  Google Scholar 

  63. Soliman AA, Mohamed GG (2004) Thermochim Acta 421:151–159

    Article  CAS  Google Scholar 

  64. Raman N, Raja SJ, Joseph J, Raja JD (2007) Russ J Coord Chem 33:7–11

    Article  CAS  Google Scholar 

  65. Mathieu M, Van Der Voort P, Weckhuysen BM, Rao RR, Catana G, Schoonheydt RA, Vansant EF (2001) J Phys Chem B 105:3393–3399

    Article  CAS  Google Scholar 

  66. Pessoa JC, Cavaco I, Correia I, Costa D, Henriques RT, Gillard RD (2000) Inorg Chim Acta 305:7–13

    Article  Google Scholar 

  67. Ghosh T, Bandyopadhyay C, Bhattacharya S, Mukherjee G (2004) Transit Metal Chem 29:444–450

    Article  CAS  Google Scholar 

  68. Dutta SK, Kumar SB, Bhattacharyya S, Tiekink ERT, Chaudhury M (1997) Inorg Chem 36:4954–4960

    Article  CAS  Google Scholar 

  69. Stepanenko IN, Krokhin AA, John RO, Roller A, Arion VB, Jakupec MA, Keppler BK (2008) Inorg Chem 47:7338–7347

    Article  PubMed  CAS  Google Scholar 

  70. Wild S, Roglic G, Green A, Sicree R, King H (2004) Diabetes Care 27:1047–1053

    Article  PubMed  Google Scholar 

  71. Lee S, Wang Q (2006) Med Res Rev 27:553–573

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported financially by the National Natural Science Foundation of China (grant no. 20471033), the Natural Science Foundation of Shanxi Province (grant no. 20051013), the Overseas Returned Scholar Foundation of Shanxi Province of China in 2006 and 2008, and University of Massachusetts Dartmouth, MA, USA.

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Authors and Affiliations

  1. Institute of Molecular Science, The Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, 92 Wucheng Road, 030006, Taiyuan, China

    Caixia Yuan, Liping Lu, Xiaoli Gao, Yanbo Wu & Miaoli Zhu

  2. Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, Dartmouth, MA, 02747, USA

    Liping Lu & Maolin Guo

  3. Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, 130023, Changchun, China

    Ying Li & Xueqi Fu

  4. State Key Laboratory of Coordination Chemistry, Nanjing University, 210093, Nanjing, China

    Miaoli Zhu

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  1. Caixia Yuan
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Correspondence to Liping Lu, Maolin Guo, Xueqi Fu or Miaoli Zhu.

Electronic supplementary material

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775_2009_496_MOESM1_ESM.pdf

Supplementary material 1 Supporting Information Available: X-ray crystallographic data in CIF format of complex 1 (CCDC708872) and 2 (CCDC707122). These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk. Detailed information on the crystal data and structure determination (Table S1), Selected bond lengths and angles for complexes 1 and 2 (Table S2), Unit cell packing diagrams for complexes 1 and 2 (Figs. S1 and S2), UV–vis data for the ligands and the complexes (Table S3), ESI-MS data (Figs. S3, A-E) and molecular modeling of the interactions of complex 2 at the active site of PTP1B (Figs. S4 and S5). (PDF 619 kb)

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Yuan, C., Lu, L., Gao, X. et al. Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities. J Biol Inorg Chem 14, 841–851 (2009). https://doi.org/10.1007/s00775-009-0496-6

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