Activation of trans-palladiums for antitumour activity
M.E.H. Mazumder Discipline of Biomedical Science, The University of Sydney, Australia
Abstract:
Cisplatin constitutes a cornerstone for the treatment of various solid tumours. The problems of systemic toxicity and resistance to cisplatin have spurred researchers to design new platinums and nonplatinums aiming to overcome such limitations. Among the nonplatinums, trans-palladium compounds have shown promising cytotoxicity in recent years. In this work, three planaraminepalladium (II) complexes of the form trans-PdCl2L2, coded as EH1, EH3, and EH4 (where L=2-methyl pyridine, imidazole, and 1,2-α-imidazopyridine respectively) have been synthesized and characterized by elemental analysis, IR, NMR and MS spectral studies. Cytotoxicity of the designed palladiums (alone or in combination with cisplatin) against ovarian cancer cell lines was determined using MTT assay. The nature of interaction of the compounds with salmon sperm DNA and pBR322 plasmid DNA was also investigated using gel-electrophoresis. The IC50 values (in µM) as applied to A2780, A2780CisR, and A2780ZD0473R ovarian cancer cell lines were respectively: cisplatin - 0.78, 5.75, and 2.90; EH1 - 34.73, 27.23 and 25.02; EH3 - 32.16, 25.15 and 25.25; EH4 - 6.78, 7.95 and 6.03. Although the designed palladiums are less active than cisplatin, they should be seen to possess considerable activity. The results indicate that the introduction of bulky planaramine ligands have made the compounds less reactive and consequently tumour active. The compounds have much lower resistance factors than cisplatin. This poster will also describe the results including those from DNA binding studies and binary combinations of cisplatin with the designed palladiums.
Keywords: Cisplatin, trans-palladiums, cytotoxicity, DNA binding
