ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P174. Non-Covalent Metallo-Drugs Coupled to Sex Hormone Steroids
C. Sanchez Cano a , A. Gómez Quiroga b , C. Navarro Ranninguer b , M. Hannon a
a School of Chemistry, University of Birmingham, , B15 2TT, Birmingham, United Kingdom
b Departamento de Química Inorganica, Universidad Autonoma de Madrid, , 28049, Madrid, Spain
e-mail: cxs527@bham.ac.uk
Different biomolecules have been used in the last years as delivery vectors with varying degrees of succes. Sex
hormones such as estrogens and testoteron are of interest as vectors because of their importance in the
development and treatment of reproductive system cancers (a high number show over-expression of steroid
receptors). Conjugates of metallo-drug units and bioactive steroids have therefore been created with the aim of
localizing cytotoxic drugs[1, 2]. Almost all of these previous bioconjugates have focused on DNA alkylating
agents that form a direct covalent or coordinate bond to the bases like cisplatin.
Non-covalent DNA-binding metallo-drugs have been extensively studied, and showing a broad spectrum of
direct activities[3, 4, 5] they represent an interesting alternative to covalent DNA-binders, because their different
mode of action can circunvent some problems, such as cross-resistance or side effects.
For this reason we have explored conjugating non-covalent metallo-drug units to steroids. Our approach is to
attach an intercalating Pt(II) terpyridine moeity to estradiol and testosterone units. Synthetic techniques and
approaches that allow very easy accests to such conjugates will be described. We show that these
metallointercalator-steroids conjugates are potent cytotoxic agents. They also possess interesting fluorescence
properties, demostrating fluorescent enhancement on interaction with DNA.
References:
[1] A. Jackson, J. Davis, R.J. Pither, A. Rodger and M.J. Hannon, Inorg. Chem., 2001, 40, 3964-73.
[2] M.J. Hannon, P.S. Green, D.M. Fisher, P.J. Derrick, J.L. Beck, S.J. Watt, M.M. Sheil, P.R. Barker, N.W.
Alcock, R.J. Price, K.J. Sanders, R. Pither, J. Davis and A. Rodger, Chem. - Eur. J., 2006, 12, 8000-8013.
[3] A. Oleksy, A.G. Blanco, R. Boer, I. Usón, J. Aymami, A. Rodger, M.J. Hannon and M. Coll, Angew. Chem.,
Intl. Ed., 2006, 45, 1227-1231.
[4] G. I. Pascu, A. C. G. Hotze, C. Sanchez Cano, B. M. Kariuki, M. J. Hannon, Angew. Chem., Intl. Ed., 2007,
46, 4374-4378.
[5] D. Ma, T. Y. Shum, F. Zhan, C. Che, M. Yang, Chem. Commun., 2005, 4675-4677.
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