2. Academic Validation
  3. A New Approach in Cancer Treatment: Discovery of Chlorido[ N, N'-disalicylidene-1,2-phenylenediamine]iron(III) Complexes as Ferroptosis Inducers

A New Approach in Cancer Treatment: Discovery of Chlorido[ N, N'-disalicylidene-1,2-phenylenediamine]iron(III) Complexes as Ferroptosis Inducers

  • J Med Chem. 2019 Sep 12;62(17):8053-8061. doi: 10.1021/acs.jmedchem.9b00814.
Jessica Sagasser 1,  Benjamin N Ma 1,  Daniel Baecker 1,  Stefan Salcher 2,  Martin Hermann 3,  Julia Lamprecht 2,  Stefanie Angerer 2 4,  Petra Obexer 2 5,  Brigitte Kircher 2 4,  Ronald Gust 1
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI-Center for Molecular Biosciences Innsbruck , University of Innsbruck, CCB-Center for Chemistry and Biomedicine , Innrain 80-82 , 6020 Innsbruck , Austria.
  • 2 Tyrolean Cancer Research Institute , Innrain 66 , 6020 Innsbruck , Austria.
  • 3 Department of Anesthesiology and Critical Care Medicine , Medical University Innsbruck , Anichstraße 35 , 6020 Innsbruck , Austria.
  • 4 Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology) , Medical University Innsbruck , Anichstraße 35 , 6020 Innsbruck , Austria.
  • 5 Department of Pediatrics II , Medical University Innsbruck , Innrain 66 , 6020 Innsbruck , Austria.
PMID: 31369259 DOI: 10.1021/acs.jmedchem.9b00814
Abstract

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) complexes generate lipid-based ROS and induce Ferroptosis in leukemia and neuroblastoma cell lines. The extent of Ferroptosis on the mode of action is regulated by simple modifications of the substituents at the 1,2-phenylenediamine moiety. In HL-60 cells, the unsubstituted lead exclusively caused Ferroptosis. For instance, a 4-F substituent shifted the mode of action toward both Ferroptosis and Necroptosis, while the analogously chlorinated derivative exerted only Necroptosis. Remarkably, cell-death in NB1 neuroblastoma cells was solely induced by Ferroptosis, independent of the used substituents. The effects were higher than that of the therapeutically applied drug cisplatin. These data clearly demonstrate for the first time that not only iron ions but also iron salophene complexes are potent Ferroptosis inducers, which can be optimized as antitumor agents.

Figures
Products