- Studies on the Synthesis and Characterization, and Binding with DNA of Two Cis-Planaramineplatinum(II) Complexes of the Forms: Cis-PtL₂Cl₂ and Cis-PtL(NH₃)Cl₂ and Where L=3-Hydroxypyridine and Imidazo(1,2-a) Pyridine

Fazlul Huq*¹, Ahmed Abdullah¹, Ashraf Chowdhury¹, Hasan Tayyem¹, Philip Beale² and Keith Fisher³

¹School of Biomedical Sciences, Cumberland Campus, C42, The University of Sydney, Australia. f.huq@fhs.usyd.edu.au

²RPAH, Missenden Road, Camperdown NSW, Australia

³School of Chemistry, F11, University of Sydney, NSW 2006, Australia

Abstract: Two cis-planaramineplatinum(II) complexes: cis-bis(3-hydroxypyridine)dichloro platinum(II) (code named AH4) and cis-{imidazo(1,2-a)pyridine}(ammine)dichloroplatinum(II) (code named AH5) have prepared and characterised based on elemental analyses, IR, Raman, mass and ¹H NMR spectral measurements. The interactions of the compounds with salmon sperm and pBR322 plasmid DNAs have been investigated. The compounds are believed to form mainly monofunctional N7(G) and bifunctional intrastrand N7(G)N7(G) adducts with DNA, causing a local distortion of DNA as a result of which gel mobility of the DNA changes. Both the compounds are less active than cisplatin against ovarian cancer cell lines: A2780, A2780^cisR and A2780^ZD0473R. The compounds are found to cause some prevention of BamH1 digestion which is believed to be due to the formation of intrastrand bifunctional Pt(GG) adducts. The compounds are also found to cause damage to pBR322 plasmid DNA, AH4 being more damaging than AH5, possibly due to greater stacking interaction involving planaramines.

Keywords:       Cisplatin; transplatin; 3-hydroxypyridine; imidazo(1,2-α)pyridine; gel electrophoresis; pBR322 plasmid DNA; anticancer activity

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