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Aminosalicylic acid conjugates of EDTA as potential anti-inflammatory pro-drugs: synthesis, copper chelation and superoxide dismutase-like activities

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Abstract

Aminosalicylic acids have been used to combat inflammatory bowel diseases (IBDs) for over 60 years. In this report, spectroscopic studies on the Cu(II) complexation behaviour of the newly synthesised chelator ethylenediaminetetraacetic acid bis-(4-aminosalicylic acid methyl ester) (4-EBAME), and the regiostereoisomer ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) (5-EBAME) are presented. Both conjugates bind to Cu(II) in an ideal 1:1 ratio, as shown by Job’s method and spectroscopic titrations. 5-EBAME was screened in the NCI 60 cancer cell-line and showed anti-cancer properties. Neither of the conjugates were degraded by bovine liver protease, although some de-esterification was seen at high pH over a 24-h period. These two conjugates show potential as metal chelating anti-oxidants for use against IBDs.

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Acknowledgements

We would like to thank the University of Brighton for financial support, the Mass Spectrometry Service at the University of Swansea and the National Cancer Institute (NCI) for carrying out the cancer screening.

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Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building Moulsecoomb, Brighton, BN2 4GJ, UK

    Mark A. Bailey, Matthew J. Ingram, Ken J. Rutt & Howard T. Dodd

  2. School of Life Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK

    Declan P. Naughton

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  1. Mark A. Bailey
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  2. Matthew J. Ingram
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  3. Declan P. Naughton
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  4. Ken J. Rutt
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  5. Howard T. Dodd
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Correspondence to Matthew J. Ingram.

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Bailey, M.A., Ingram, M.J., Naughton, D.P. et al. Aminosalicylic acid conjugates of EDTA as potential anti-inflammatory pro-drugs: synthesis, copper chelation and superoxide dismutase-like activities. Transition Met Chem 33, 195–202 (2008). https://doi.org/10.1007/s11243-007-9031-1

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  • DOI: https://doi.org/10.1007/s11243-007-9031-1

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