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Issue 33, 2016
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Towards 99mTc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study

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Abstract

Doxorubicin is a clinical benchmark drug, which is applied in the treatment of numerous cancers. Known for its accumulation in the nucleus and ability to intercalate into DNA, it targets quickly dividing i.e. hypermitotic cells. Through this mechanism, it could be an ideal structural motif for a new class of imaging agents, given that the new entity approximates the in vitro profile of the parent drug. Here we describe design, synthesis and biological activity of a small array of Doxorubicin-metalloconjugates (M = 99mTc, Re). We demonstrate that the conjugates preferably accumulate in the nuclear compartment, tightly bind to DNA and retain an appreciable cytotoxicity. Moreover, the Re conjugates effectively act as inhibitors of the human Topoisomerase II enzyme, which is the widely accepted mechanism of action of the parent drug. Since the conjugates effectively mimic the in vitro behavior of native Doxorubicin, the 99mTc compounds are prospective imaging agents.

Graphical abstract: Towards 99mTc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study

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Publication details

The article was received on 04 Mar 2016, accepted on 08 Apr 2016 and first published on 08 Apr 2016


Article type: Communication
DOI: 10.1039/C6DT00871B
Citation: Dalton Trans., 2016,45, 13025-13033
  • Open access: Creative Commons BY license
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    Towards 99mTc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study

    S. Imstepf, V. Pierroz, P. Raposinho, M. Felber, T. Fox, C. Fernandes, G. Gasser, I. R. Santos and R. Alberto, Dalton Trans., 2016, 45, 13025
    DOI: 10.1039/C6DT00871B

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