Synthesis, cytotoxicity, and insight into the mode of action of Re(CO)3 thymidine complexes

ChemMedChem
Mark D BartholomäJon Zubieta

Abstract

Nucleoside analogues are extensively used in the treatment of cancer and viral diseases. The antiproliferative properties of organorhenium(I) complexes, however, have been scarcely explored to date. Herein we present the syntheses, characterization, and in vitro evaluation of Re(I)(CO)(3) core complexes of thymidine and uridine. For the binding of the Re(I)(CO)(3) core, a tridentate dipicolylamine metal chelate was introduced at positions C5', C2', N3, and C5 with spacers of various lengths. The corresponding organometallic thymidine complexes were fully characterized by IR and NMR spectroscopy and mass spectrometry. Their cytotoxicity was assessed against the A549 lung carcinoma cell line. Toxicity is dependent on the site and mode of conjugation as well as on the nature and the length of the tether. Moderate toxicity was observed for conjugates carrying the rhenium moiety at position C5' or N3 (IC(50)=124-160 microM). No toxicity was observed for complexes modified at C2' or C5. Complex 53, with a dodecylene spacer at C5', exhibits remarkable toxicity and is more potent than cisplatin, with an IC(50) value of 6.0 microM. To the best of our knowledge, this is the first report of the antiproliferative properties of [M(CO)(3)](+...Continue Reading

References

Dec 2, 1992·Journal of the National Cancer Institute·K L O'NeillG W Odling-Smee
Jun 5, 1991·Journal of the National Cancer Institute·A MonksA Vaigro-Wolff
Jul 19, 1995·Biochimica Et Biophysica Acta·B Munch-PetersenK Eger
Aug 5, 1996·Biochemical and Biophysical Research Communications·S Gerber, G Folkers
Jul 25, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·W Pretsch
Feb 22, 2001·Nuclear Medicine and Biology·O GardelleB Kaser-Hotz
Jan 26, 1996·The Journal of Organic Chemistry·Danny P. C. McGeeYansheng Zhai
Oct 5, 2002·Cellular and Molecular Life Sciences : CMLS·S ErikssonH Eklund
Sep 5, 2003·Cancer Biotherapy & Radiopharmaceuticals·Inga BuchmannSven N Reske
Dec 10, 2003·Oncogene·Deepa SampathWilliam Plunkett
Dec 20, 2003·Organic & Biomolecular Chemistry·Jian GaoArthur E Martell
Dec 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Martin WelinHans Eklund
Mar 29, 2005·Inorganic Chemistry·Lihui WeiJon Zubieta
Jan 6, 2006·Environmental and Molecular Mutagenesis·Ofelia A Olivero
Feb 27, 2007·Journal of the American Chemical Society·Anna F A PeacockPeter J Sadler
Oct 19, 2007·ChemMedChem·Jian GaoRalph A Zingaro
Apr 29, 2008·Bioorganic & Medicinal Chemistry·Feng LiShigetoshi Kadota
Jan 17, 2009·Inorganic Chemistry·Sabine H van RijtPeter J Sadler
Apr 30, 2009·Inorganic Chemistry·Harriet StruthersRoger Schibli

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Citations

Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Mark Daniel BartholomäJon Zubieta
Apr 27, 2013·Future Medicinal Chemistry·Ahmed KhalilWerner Tjarks
Mar 4, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Mark D BartholomäJon Zubieta
Aug 20, 2014·ACS Chemical Biology·Anna Leonidova, Gilles Gasser
Nov 8, 2014·Chemistry : a European Journal·Sylvain Clède, Clotilde Policar
Jan 28, 2014·Chemistry : a European Journal·Igor KitanovicGilles Gasser
Nov 29, 2013·Mass Spectrometry Reviews·Ed Dudley, Liz Bond
Mar 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying-Cheng HuangChung-Shan Yu
Jul 25, 2017·The Journal of Physical Chemistry. a·F Y AdeowoA A Skelton
Jan 8, 2014·Journal of Labelled Compounds & Radiopharmaceuticals·Michael P CooganJon Zubieta
Sep 3, 2019·Current Pharmaceutical Design·Philippe ColleryVeena Vijaykumar
Aug 29, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Anna LeonidovaGilles Gasser

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