Photocytotoxic trans-diam(m)ine platinum(IV) diazido complexes more potent than their cis isomers

Nicola J. Farrer, Julie A. Woods, Vivienne P. Munk, Fiona S. Mackay, Peter J. Sadler

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    Abstract

    The photocytotoxicity of a series of anticancer trans-dihydroxido [Pt(N-3)(2)(OH)(2)(NH3)(X)] (X = alkyl or aryl amine) piatinum(IV) diazido complexes has been examined, and the influence of cis-trans isomerism has been investigated. A series of photoactivatable Pt-IV-azido complexes has been synthesized: The synthesis, characterization, and photocytotoxicity of six mixed-ligand ammine/amine Pt-IV diazido complexes, cis,trans,cis-[Pt(N-3)(2)(OH)(2)(NH3)(X)] where X = propylarnine (4c), butylamine (5c), or pentylamine (6c) and aromatic complexes where X = pyridine (7c), 2-methylpyridine (8c), or 3-methylpyridine (9c) are reported. Six all-trans isomers have also been studied where X = methylamine (2t), ethylamine (3t), 2-methylpyridine (8t), 4-methylpyridine (10t), 3-methylpyridine (9t), and 2-bromo-3-methylpyridine (11t). All of the complexes exhibit intense azide-to-Pt-IV LMCT bands (ca. 290 nm for trans and ca. 260 nm for cis). When irradiated with UVA light (365 nm), the Pt-IV complexes undergo photoreduction to Pt-II species, as monitored by UV-vis spectroscopy. The trans isomers of complexes containing aliphatic or aromatic amines were more photocytotoxic than their cis isomers. One of the cis complexes (9c) was nonphotocytotoxic despite undergoing photoreduction. Substitution of NH3 ligands by MeNH2 or EtNH2 results in more potent photocytotoxicity for the all-trans complexes. The complexes were all nontoxic toward human keratinocytes (HaCaT) and A2780 human ovarian cancer cells in the dark, apart from the 3-methylpyridine (9t), 2-bromo-3-methylpyridine (11t), and 4-methylpyridine (10t) derivatives.

    Original languageEnglish
    Pages (from-to)413-421
    Number of pages9
    JournalChemical Research in Toxicology
    Volume23
    Issue number2
    Early online date8 Dec 2009
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • Heterocyclic amine ligand
    • Anticancer complexes
    • In vitro
    • Structural characterization
    • Photodynamic therapy
    • Transplatin analogs
    • DNA interactions
    • Comet assay
    • One planar
    • Cisplatin

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