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Platinum(II) chloride indenyl complexes: electrochemical and biological evaluation

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Abstract

Four platinum(II) complexes of general formula [PtCl(η1-C9H7)L2] [where L2 is 1,2-bis(diphenylphosphino)ethane (dppe) 1 or cycloocta-1,5-diene (cod) 3] and [PtCl2L2] (where L2 is dppe 2 or cod 4) were studied. Inhibition growth assays on human tumor cell lines evidenced for 1 and 3 an antiproliferative effect and, interestingly, the cytotoxic effect exerted by 1 is similar to that of cisplatin. Electrochemical and NMR measurements allowed us to determine the structural and redox properties. Investigation of the mechanism of action responsible for the cytotoxicity demonstrated a weak capacity of interacting with DNA. Some experiments performed on rat liver mitochondria indicate that 1 acts as an inducer of the mitochondrial permeability transition, thus leading to the release of proapoptotic factors, such as cytochrome c and apoptosis-inducing factor.

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Abbreviations

AIF:

Apoptosis-inducing factor

cod:

Cycloocta-1,5-diene

COSY:

Correlation spectroscopy

CsA:

Cyclosporin A

CV:

Cyclic voltammetry

dach:

1,2-Diaminocyclohexane

DMSO:

Dimethyl sulfoxide

dppe:

1,2-Bis(diphenylphosphino)ethane

EGTA:

Ethylene glycol bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid

EXSY:

Exchange spectroscopy

FITC:

Fluorescein isothiocyanate

HEPES:

N-(2-Hydroxyethyl)piperazine-N′-ethanesulfonic acid

ICP-AES:

Inductively coupled plasma atomic emission spectroscopy

MPT:

Mitochondrial permeability transition

NEM:

N-Ethylmaleimide

NOESY:

Nuclear overhauser effect spectroscopy

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

RLM:

Rat liver mitochondria

SCE:

Standard calomel electrode

SDS:

Sodium dodecyl sulfate

TBS:

2 mM tris(hydroxymethyl)aminomethane–HCl, 13.7 mM NaCl, pH 7.6

TE:

10 mM tris(hydroxymethyl)aminomethane, 1 mM EDTA, pH 7.4

THF:

Tetrahydrofuran

TMRM:

Tetramethylrhodamine methyl ester

Tris:

Tris(hydroxymethyl)aminomethane

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Acknowledgments

Massimiliano Imhoff and Annalisa Bisello are gratefully acknowledged for their expert assistance in the synthesis and electrochemical measurements.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Padova, Via F. Marzolo, 5, 35131, Padua, Italy

    Lisa Dalla Via

  2. Department of Chemical Sciences, University of Padova, Via F. Marzolo, 1, 35131, Padua, Italy

    Saverio Santi & Vito Di Noto

  3. CNR-ISTM, Institute of Molecular Sciences and Technologies, Via F. Marzolo, 1, 35131, Padua, Italy

    Alfonso Venzo

  4. Department of Biochemical Sciences, Institute of Molecular Biology and Pathology, University of Rome “La Sapienza” and CNR, Rome, Italy

    Enzo Agostinelli

  5. Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy

    Annarica Calcabrini & Maria Condello

  6. Department of Biological Chemistry, University of Padova, Via G. Colombo, 3, 35121, Padua, Italy

    Antonio Toninello

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  1. Lisa Dalla Via
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Corresponding author

Correspondence to Vito Di Noto.

Electronic supplementary material

Below is the link to the electronic supplementary material.

775_2011_771_MOESM1_ESM.pdf

The electronic supplementary material includes NMR characterization; electrochemical data; linear and circular dichroism spectra. (PDF 279 kb)

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Dalla Via, L., Santi, S., Di Noto, V. et al. Platinum(II) chloride indenyl complexes: electrochemical and biological evaluation. J Biol Inorg Chem 16, 695–713 (2011). https://doi.org/10.1007/s00775-011-0771-1

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  • DOI: https://doi.org/10.1007/s00775-011-0771-1

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