4.7 Article

Anticancer Activity and Catalytic Potential of Ruthenium(11)-Arene Complexes with N,O-Donor Ligands

Journal

INORGANIC CHEMISTRY
Volume 57, Issue 13, Pages 7558-7567

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.8b00346

Keywords

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Funding

  1. INRS-Institut Armand-Frappier
  2. Natural Sciences and Enginneering Research Council of Canada
  3. Fonds de Recherche en Sante du Quebec (Etablissement de Jeunes Chercheurs)
  4. Canada Foundation for Innovation (John Evans Leaders Fund)
  5. Armand-Frappier Foundation (Banque Nationale Scholarship)

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The special ability of organometallic complexes to catalyze various transformations might offer new effective mechanisms for the treatment of cancer. Studies that report both the biological properties and the ability of metallic complexes to promote therapeutically relevant catalytic reactions are limited. Herein, we report the anticancer activity and catalytic potential of some ruthenium(II)-arene complexes bearing bidentate Schiff base ligands (2a and 2b) and their reduced analogues (5a and 5b, respectively). In comparison to their Schiff base counterparts 2a and 2b, we demonstrate that amine complexes 5a and 5b display (i) a higher in vitro antiproliferative activity on different human cancer cell lines, (ii) a lower rate of hydrolysis, and (iii) an improved initial catalytic rate for the reduction of NAD(+) to NADH. In contrast to their imine analogues 2a and 2b, we also show that amine complexes 5a and 5b induce the generation of intracellular reactive oxygen species (ROS) in MCF-7 breast cancer cells. Our results highlight the impact that a simple ligand modification such as the reduction of an imine moiety can have on both the catalytic and biological activities of metal complexes. Moreover, the ruthenium complexes reported here display some antiproliferative activity against T47D breast cancer cells, known for their cis-platin resistance.

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