RESEARCH ARTICLE

 

Synthesis and antitumour activity of gold(I) and silver(I) complexes of hydrazine-bridged diphosphine ligands

 

 

Frederik H. Kriel^{I, II}; Judy Coates^I

^IBiomed, Mintek, Private BagX3015, Randburg, 2125, South Africa
^IISchool of Chemistry, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa

 

 

---

ABSTRACT

A known synthetic route was used to prepare two known hydrazine-bridged phosphine ligands and four new ligands with variable groups on the hydrazine bridge (methyl and ethyl), as well as positions on the aryl phosphine groups (phenyl, methoxyphenyl, dimethylaminophenyl). A range of gold(I) and silver(I) complexes were synthesized utilizing these phosphine ligands. Both the phosphine-bridged dimetal and cationic bis(diphosphine) metal complexes were isolated. An interesting phenomenon of the spontaneous oxidation of gold(I) to gold(III) (and reduction of gold(IIII) to gold(I)) upon complexation with ((N,N-dimethyl)-4-aminophenyl)dialkylhydrazine ligands is described. Thirteen of the synthesized complexes were subjected to anticancer activity screening against HeLa, Jurkat, A2780, cisplatin-resistant A2780, CoLo 320 DM and MCF7. Most of the complexes were found to inhibit the cancerous cells at low µM concentrations and in some cases nM concentrations. Two of the complexes were tested for their ability to reduce the mitochondrial membrane potential of PBMC cells as a possible mechanism of action of anticancer activity.

Keywords: Gold(I), silver(I), hydrazine, diphosphine, antitumour, anticancer, mitochondrial membrane potential

---

 

 

Full text available only in PDF format.

 

Acknowledgements

The authors would like to thank AuTEK Biomed (Mintek and Harmony) for financial support. The University of the Witwatersrand for use of their facilities. The Department of Pharmacology at the University of Pretoria; Prof. Connie Medlen, Dr. Gizella Joone and Mrs. Margo Nell, for their guidance and the use of their facilities. Prof. Denver Hendricks at the University of Cape Town for advice and guidance.

 

References

1 D. Wang, S.J. and Lippard, Nat. Rev. Drug Discovery 4, 2005, 307-320.         [ Links ]

2 T.M. Simon, D.H. Kunishima, G.J. Vibert and A. Lorber, Cancer, 44, 1979, 1965-1975.         [ Links ]

3 E.R.T. Tiekink, Crit. Rev. Oncol./Hematol, 42, 2002, 225-248.         [ Links ]

4 J.C. Dabrawiak, Metals in Medicine, Chapter 6.2, Wiley, 205-217, 2009.         [ Links ]

5 G. Jaouen and N. Metzler-Nolte, eds., Medicinal Organometallic Chemistry, Springer, 2010.         [ Links ]

6 I. Ott, Coord. Chem Rev., 2009, 253, 1670-1681.         [ Links ]

7 S. Nobili, E. mini, I. Landini, C. Gabbiani, A. Casini and L. Messori, Med. Res. Rev., 2010, 30,550-580.         [ Links ]

8 M.J. McKeage, L. Maharaj and S.J. Berners-Price, Coord. Chem. Rev. 2002, 232, 127-135.         [ Links ]

9 S.J. Berners-Price and P.J. Sadler, Struc. and Bond., 1988, 70, 27-102.         [ Links ]

10 S.J. Berners-Price, Chem. Aust. (2004), 71, 10-12.         [ Links ]

11 S.J. Berners-Price and A. Filipovska, Metallomics, 2011, 3, 863-873.         [ Links ]

12 M.J. McKeage, S.J. Berners-Price, P. Galettis, R.J. Bowen, W. Brouwer, L. Ding, L. Zhuang and B.C. Baguley, Cancer Chemother. Pharmacol., 2000, 46, 343-350.         [ Links ]

13 J.S. Modica-Napolitano and J.R. Aprille, Advan. Drug Deliv. Rev., 2001, 49, 63-70.         [ Links ]

14 J.F. Nixon, J. Chem. Soc. A, 1968, 2689-2692.         [ Links ]

15 A.R. Davies, A.T. Dronsfield, R.N. Haszeldine and D.R. Taylor, J. Chem. Soc., Perkin Trans. I, 1973, 379-385.         [ Links ]

16 R. Jefferson, J.F. Nixon, T.M. Painter, R. Keat and L. Stubbs, J. Chem. Soc., Dalton Trans., 1973, 1414-1419.         [ Links ]

17 M.S. Balakrishna, V.S. Reddy, S.S. Krishnamurthy, J.C.T.R. Burckett St. Laurent and J.F. Nixon, Coord. Chem. Rev., 1994, 129, 1-90.         [ Links ]

18 V.S. Reddy and K.V. Katti, C.L. Barnes, Inorg. Chem., 1995, 34, 5483-5488.         [ Links ]

19 VS. Reddy and K.V. Katti, Inorg. Chem., 1994, 33, 2695-2696.         [ Links ]

20 V.S. Reddy, K.V. Katti and C.L. Barnes, Chem. Ber., 1994, 127, 1355-1357.         [ Links ]

21 A.M.Z. Slawin, M. Wainright and J.D. Woollins, J. Chem. Soc., Dalton Trans., 2002, 513-519.         [ Links ]

22 F.H. Kriel, M.A. Fernandes and J. Caddy, Acta Cryst..2010, E66, o1270.         [ Links ]

23 F.H.Kriel, M.A.Fernandes and J. Coates, ActaCryst. 2011, E67,m1426.         [ Links ]

24 S.J. Berners-Price, P.S. Jarrett and P.J. Sadler, Inorg. Chem., 1987, 26, 3074-3077.         [ Links ]

25 S.J. Berners-Price, C. Brevard, A. Pagelot and P.J. Sadler, Inorg. Chem., 1985, 24, 4278-4281.         [ Links ]

26 S.J. Berners-Price, R.K. Johnson, A.J. Giovenella, L.F. Faucette, C.K. Mirabelli and P.J. Sadler, J. Inorg. Biochem, 1988, 33, 285-295.         [ Links ]

27 H.G.R. Thompson, J.W. Harris, B.J. Wold, F. Lin and J.P. Brody, Oncogene, 2003, 22, 2322-2333.         [ Links ]

28 P.E. Bernardi, Biochim. Biophys. Acta 1366 (1998) 1-234.         [ Links ]

29 G.S. Salvesen and V.M. Dixit, Cell 91 (1997) 443-446.         [ Links ]

30 L.B. Chen, Annu. Rev. Cell Biol, 4 (1988) 155-181.         [ Links ]

31 R. Uson, A. Laguna and J. Vicente, J. Organomet. Chem., 1977, 131, 471-475.         [ Links ]

32 F.H. Kriel, M.A. Fernandes and J. Coates, Acta Cryst., 2011, E67, m42.         [ Links ]

33 F.H. Kriel, M.A. Fernandes and J. Coates, Acta Cryst., 2011, E67, m155.         [ Links ]

34 F.H. Kriel, M.A. Fernandes and J. Coates, Acta Cryst., 2011, E67, m1163        [ Links ]

35 F.H. Kriel, M.A. Fernandes and J. Coates, Acta Cryst., 2010, E66, m710.         [ Links ]

36 G.D. Hoke, G.F. Rush, G.E. Bossard, J.V. McArdle, B.D. Jensen and C.K. Mirabelli, J. Biol. Chem., 1988, 263, 11203.         [ Links ]

37 A. Cassarizza, M. Baccarani-Contri, G. Kalashnikova and C. Franceschi, Biochem. Biophys. Res. Commun., 1993, 197, 40-45.         [ Links ]

 

 

Received 13 August 2012
Revised 10 October 2012
Accepted 7 November 2012

 

 

* To whom correspondence should be addressed. E-mail: erikk@mintek.co.za