NDLI: Towards $^{99m}Tc-based$ imaging agents with effective doxorubicin mimetics: a molecular and cellular study

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fox, T. Alberto, R. Gasser, G. Fernandes, C. Pierroz, V. Santos, I. R. Imstepf, S. Felber, M. Raposinho, P.
Description	Author Affiliation: Imstepf S ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.); Pierroz V ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland and Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.); Raposinho P ( Centro de Ciências e Tecnologias Nucleares, Universidade de Lisboa, Estrada Nacional 10, PT-2695-066 Bobadela LRS, Portugal.); Felber M ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.); Fox T ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.); Fernandes C ( Centro de Ciências e Tecnologias Nucleares, Universidade de Lisboa, Estrada Nacional 10, PT-2695-066 Bobadela LRS, Portugal.); Gasser G ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.); Santos IR ( Centro de Ciências e Tecnologias Nucleares, Universidade de Lisboa, Estrada Nacional 10, PT-2695-066 Bobadela LRS, Portugal.); Alberto R ( Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.)
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 = $^{99m}Tc,$ 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 $^{99m}Tc$ compounds are prospective imaging agents.
ISSN	14779226
Issue Number	33
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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