Book of Abstracts - Ruhr-Universität Bochum

OP-20
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
DNA and Protein Binding, Cleavage and Anticancer Activity of Organometallic
(M = Ru(II), Rh(III) and Ir(III)) Arene Complexes
R. Loganathan, a S. Ramakrishnan, a P. Kumar, c D. S. Pandey, c A. Riyasdeen, b
M. A. Akbarsha, b and Mallayan Palaniandavar* a
a Centre for Bioinorganic Chemistry, School of Chemistry, b Department of Animal Science,
Bharathidasan University, Tiruchirapalli 620 024, India. c Department of Chemistry, Facult of
Science, Banaras Hindu University, Varanasi 221 005, India.
E-mail: palanim51@yahoo.com
The study of organometallic compounds as anticancer agents is receiving much attention now. These
compounds can be tuned by using suitable chelating ligands to facilitate their uptake into the cells or
for selectivity of reactions with DNA or proteins. However, the number of such studies is very limited.
This is because of the low solubility and instability in water and poor uptake by the cells. The
ruthenium complexes NAMI-A and KP1019, which show prominent anticancer activity, are currently
in clinical trials for the treatment of metastasis and colorectal cancers, respectively. Very recently, we
have shown that non-covalent interactions of certain water soluble Ru(II) complexes 1,2 with DNA
enhances the cytotoxicity against several cancer cell lines. It is noteworthy that a family of
ruthenium(II)–arene complexes developed by Sadler, and Dyson et al. exhibits high in vitro and in
vivo anticancer activity. The titanocene dichloride has already completed phase II clinical trials and
ferrocifen, which is a ferrocenyl derivative of tamoxifen, appears set to enter clinical trials soon. More
recently, increasing interest has been focused on organometallic-arene compounds, which show
excellent antiproliferative properties in vitro and in vivo. In this work a series of water soluble
organometallic complexes of the type [{Ru(η 6 -arene)(L)Cl}](BF4)2 (arene = benzene; 1 and p-cymene;
2) and [{(η 5 - C10Me5)M(L)Cl}](BF4)2, (M = Rh; 3 and Ir; 4 and L = benzyl-di-pyridin-2-yl-amine) has
been isolated and the structures of 3 and 4 have been determined by X-ray crystallography. The
bidentate benzyl-di-pyridin-2-ylamine ligand is designed to provide hydrophobicity. Also, the present
compounds are equipped with a chloride leaving group in order to enable covalent interaction of the
complexes with biological targets. Further, the arene ligand provides hydrophobicity thus tuning the
DNA- and protein-binding and DNA- and protein-cleaving properties of the complexes. The
interactions of these metal complexes with CT DNA have been explored by using absorption,
emission and CD spectroscopy and electrochemical and viscosity measurements. DNA and protein
cleavage reactions have also been studied using agarose and polyacrylamide gel electrophoresis
respectively. The anticancer activities and the mode of cell death have also been established. The
results of our systematic investigations will be presented and discussed.
References
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1. V. Rajendiran, M. Murali, E. Suresh, S. Sinha, K. Somasundaram, M. Palaniandavar Dalton Trans.
2008, 148-163.
2. V. Rajendiran, M. Murali, E. Suresh, M. Palaniandavar, V.S. Periasamy, M.A. Akbarsha
Dalton Trans. 2008, 2157-2170.
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