Trevor W. Hambley

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Previous work has shown platinum drugs to differ in their effects on the peripheral nervous system. To test whether their differential toxicity was due to differences in their partitioning into the peripheral nervous system, we correlated the hydrophobicity, reactivity, tissue accumulation and neurotoxicity of a series of eight platinum analogues.(More)
The diaminocyclohexane platinum (Pt(DACH)) derivatives ormaplatin and oxaliplatin have caused severe and dose-limiting peripheral sensory neurotoxicity in a clinical trial. We hypothesized that this toxicity could vary in relation to the biotransformation and stereochemistry of these Pt(DACH) derivatives. We prepared pure R,R and S,S enantiomers of(More)
Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma derived from skeletal muscle precursor cells, which accounts for 5-8% of all childhood malignancies. Disseminated RMS represents a major clinical obstacle, and the need for better treatment strategies for the clinically aggressive alveolar RMS subtype is particularly apparent. Previously, we have(More)
Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal models without a priori knowledge of the(More)
The platinum(IV) complexes: [PtCl(4)(en)], cis,trans-[PtCl(2)(OAc)(2)(en)], cis,trans-[PtCl(2)(OH)(2)(en)] and trans-[Pt(OH)(2)(ethmal)(en)], encompassing a range of reduction potentials and their platinum(II) analogue [PtCl(2)(en)], have been assayed for their protein binding ability in the presence of albumin, albumin and L-cysteine and RPMI 1640 tissue(More)
Reaction of the fluoroquinolone antimicrobial ciprofloxacin with copper(II) nitrate in the presence of 2,2'-bipyridine resulted in the isolation of the complex [Cu(cip)(bipy) (Cl)0.7(NO3)0.3] (NO3).2H2O. Reaction of an aqueous solution of ciprofloxacin.HCl and NaCl with CuCl2 at pH 5.0 resulted in the isolation of [Cu(cip)2]Cl2.11H2O. The complex [Cu(cip)(More)
Gastrointestinal (GI) toxicity is one of the major problems associated with antiinflammatory drugs. The complexation of the powerful antiinflammatory drug (IndoH) by metal ions, as a means of reducing GI toxicity, has been studied. The in vitro superoxide dismutase (SOD) activity, in vivo antiinflammatory activity, and gastrointestinal ulcerogenic(More)
Four-coordinate (Pt(II)) platinum-based anticancer drugs are widely used in primary or palliative chemotherapy and produce considerable efficacy in certain clinical applications, for example testicular cancer. However, in many cancers the Pt(II) drugs are beset by poor efficacy mainly due to suboptimal pharmacokinetic properties. Consequently, the(More)