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

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Eurobic9, 2-6 September, 2008, Wrocław, Poland P121. Novel Anticancer-active Fluorescent Platinum(II) Complexes Containing Anthracene Derivatives as Carrier Ligands P. Marques-Gallego, a H. den Dulk, a J. Brouwer, a H. Kooijman, b A. L. Spek, b S. J. Teat, c J. Reedijk a * a Coordination and Bioinorganic Chemistry, Leiden Institute of Chemistry, Einsteinweg 55, 2333 CC, Leiden, Netherlands e-mail: p.marques@chem.leidenuniv.nl b Bijvoet Center for Biomolecular Research, Utrecht University c ALS, Berkeley Lab, 1 Cyclotron Rd Since the introduction of cisplatin into oncology practice, several studies dealing with molecular mechanisms of action have provided considerable and significant information about how cisplatin induces its antitumor effects. However, cellular processing of anticancer agents remains largely unknown. Several efforts have been undertaken to elucidate these mechanisms; one is the attachment of a fluorescent label to a cisplatin-derivative complex [1]. Another approach, also from our laboratory, is the use of fluorescent ligands for the synthesis of fluorescent platinum complexes [2]. Biological studies of novel fluorescence platinum(II) complexes have shown high activity against several human tumor cell lines, as compared to cisplatin. In addition, a different cellular response was found for the free ligands, as compared to their corresponding platinum(II) complexes. Therefore, these compounds are of interest for molecular and optical studies. The present contribution describes the cytotoxic activity against several human tumor cell lines and their cellular processing. References: [1] Molenaar, C., Teuben, J. M., Heetebrij, R. J., Tanke, H. J., and Reedijk, J. (2000) J. Biol. Inorg. Chem. 5, 655-665 [2] Jansen, B. A. J., Wielaard, P., Kalayda, G. V., Ferrari, M., Molenaar, C., Tanke, H. J., Brouwer, J., and Reedijk, J. (2004) J. Biol. Inorg. Chem. 9, 403-413 _____________________________________________________________________ 240
Eurobic9, 2-6 September, 2008, Wrocław, Poland P122. Novel Pt (II) Complexes with 4-nitropyrazole Derivatives Ligands A. Mastalarz a , M. Kubiak a , T. Lis a , J. Kuduk-Jaworska a , A. Regiec b , H. Mastalarz b a Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie str., 50-3<strong>83</strong> Wroclaw, Poland, b Faculty of Pharmacy , Wroclaw Medical University, 8 Grodzka str., 50-137 Wrocław, Poland The results of screenings done so far on thousands of platinum complexes towards their cytotoxicity, and on some of them towards radiosensitizing activity, are not very satisfied. The reason of the therapeutic usefulness of many screened candidates seems to be caused by inappropriate choice of the ligands, in particular N-donors which strongly modulate the biological properties of complexed compounds. Our goal was to synthesize a series of potentially radiosensitizing compounds which contain platinum (II) centre able to interact with DNA and to stabilize its damages caused by radiotherapy in the tumor cells. Amongst synthesized Pt(II) complexes of general formula PtL2Cl2 and KPtLCl3 we paid special attention on complexes with N-methyl-4-nitropyrazole, N-methyl-4-nitro-3- or –5- carbomethoxypyrazole. These ligands were chosen due to their potential electron-affinic properties [1]. In this way it might be achieved a goal of this work: to obtain complexes with dual mode of action, binding to DNA and implying electron accepting mechanism. Presented poster summarizes the results of chemical and structural investigations of new compounds by using the NMR, IR, MS spectroscopic methods and X-ray crystallography. The preliminary results of biological tests on antiproliferative properties of presented compounds are promising. References: [1]. Anna Zięba-Mizgała, Aniela Puszko, Andrzej Regiec, Janina Kuduk-Jaworska Electrophilic properties of nitroheterocyclic compounds.Potential hypoxic cells radiosensitizers. Bioelectrochemistry, 65, 113 - 119 (2005). _____________________________________________________________________ 241
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ISBN: 978-83-60043-10-3 - eurobic9

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