Book of Abstracts - Ruhr-Universität Bochum

P-01
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
In Vitro and In Vivo Anti-tumor Activities of Five Coordinated Cyclometallated
Organoplatinum(II) Complexes Containing Biphosphine Ligands
Hamidreza Samouei, a Mehdi Rashidi,* a Q. Ping Dou, *b Michael Frezza, b Yan Xiao, b
amd Frank W. Heinemann c
a Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran. b Department of
Pathology, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, Detroit,
USA. c Institut fuer Anorganische Chemie, Universitaet Erlangen-Nuernberg, Egerlandstrasse 1, D-
91058 Erlangen, Germany. E-mail:samouei@gmail.com
Ever since Rosenberg in late 1960s discovered the anti-tumor activity of cisdiamminedichloroplatinum(II),
cis-[Pt(NH3)2Cl2] known as cisplatin, 1 many other Pt complexes have
been designed, synthesized and tested in order to circumvent the cisplatin acquired resistance, side
effects, toxicity and low water solubility in order to increase the efficacy of the drug. 2 Most platinum
complexes being used as therapeutic agents usually contain amine (with at least one N-H bond)
ligands, 3 but the analogous complexes containing phosphine ligands are not unusual in these kinds of
applications. 3b,4 Many attempts have been made during the past 3 decades to synthesize new
complexes of platinum and other transition metals (such as Ru) to overcome the difficulties associated
with cisplatin. For example some cyclometallated Pt(II) complexes have recently been used as active
cytotoxic anticancer drugs. 4,5 The use of phosphine ligands instead of amines has recently been
envisaged, in particular because a large number of gold complexes containing phosphine ligands have
successfully been used as therapeutic agents. 4,6
In the present study, we report two novel cyclometallated Pt(II) complexes containing biphosphine
ligands with unique structural features that are more potent than cisplatin in relation to their anti-tumor
activity and have also been found to exhibit proteasome-inhibitory activities in vitro and in vivo. We
also have suggested a potential relationship between the structure of the complexes and their cytotoxic
effects.
References
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2. K. S. Lovejoy, S. J. Lippard, Dalton Trans. 2009, 10651-10659.
3. (a) P. J. Miguel, M. Roitzsch, L. Yin, P. M. Lax, L. Holland, O. Krizanovic, M. Lutterbeck, M.
Schurmann, E. C. Fusch, B. Lippert, Dalton Trans. 2009, 10774-10786; (b) J.C. Shi, C.H. Yueng,
D.X. Wu, Q.T. Liu, and B.S. Kang, Organomet. 1999, 18, 3796-3801.
4. R. W.Y. Sun, D. Ma, E. L. M. Wong, C. M. Che, Dalton Trans. 2007, 4884-4892.
5. T.Okada, I.M.El-Mehasseb, M.Kodaka,, T.Tomohiro, K.Okamoto, H.Okuno, J. Med. Chem. 2001,
44, 4661-4667.
6. (a) L. C. Eiter, N. W. Hall, C. S. Day,G. Saluta, G. L. Kucera, U. Bierbach, J. Med. Chem. 2009, 52,
6519-6522; (b) C. P. Bagowski, Y. You, H. Scheffler, D. H. Vlecken, D. J. Schmitz, I. Ott, Dalton
Trans, 2009, 10799-10805.
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