In this paper we report the synthesis and in vitro activity of two new mixed ligand platinum complexes: trans- [PtCl2(thiazole)(imidazole) [JH3] and trans-[PtCl2(thiazole)(3-hydroxypyridine) [JH4]. Although the compounds are less active than cisplatin against the parent ovarian cancer cell line A2780, they are more active than cisplatin against the resistant cell lines A2780cisR and A2780ZD0473R, thus indicating that JH3 and JH4 have been better able to overcome mechanisms of resistance operating in A2780cisR and A2780ZD0473R. When Pt-DNA binding levels at 24 h in A2780, A2780cisR and A2780ZD0473R cell lines are compared it is found that whereas for cisplatin the values in resistant cell lines are significantly lower than that in the parent cell line, for JH3 and JH4 Pt-DNA binding levels in the parent and resistant cell lines are comparable, thus providing an explanation for variations in activity of the compounds in the three cell lines.
Keywords: Transplatinum, ovarian cancer, drug resistance, pBR322, plasmid, Pt-DNA binding, Mixed Ligand Platinum Compounds, numerous toxic side effects, trans-planaramineplatinum complexes, 3-diaminopyridine, imidazole, JETQUICK, K2PtCl4, tetrachloroplatinate, Microanalyses, trans-planaramineplatinum(II), Molar Conductivities, KBr beamsplitter, electrospray ionization, Cytotoxicity Assays, diphenyltetrazolium bromide, quadruplicate determinations, trypsinized, Proteinase, spectrophotometry, electrophoresis, phosphodiester, resistance factors, Accumulation of Pt, cisplatin in 2, 4, trans-platinum compounds, DNA Binding, Cisplatin, monofunctional adducts, piperidine, Enzyme Digestion, pBR322 plasmid DNA
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