Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI-Center for Molecular Biosciences Innsbruck, CCB-Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria.
Int J Mol Sci. 2023 Jan 21;24(3):2173. doi: 10.3390/ijms24032173.
The [-disalicylidene-1,2-phenylenediamine]iron(III) ([salophene]iron(III)) derivatives - with anionic axial ligands (A = Cl, NO, SCN, CHCOO) and complexes and with neutral ligands (A = imidazole, 1-methylimidazole) as well as the μ-oxo dimer inhibited proliferation, reduced metabolic activity, and increased mitochondrial reactive oxygen species. Ferroptosis as part of the mode of action was identified by inhibitor experiments, together with induction of lipid peroxidation and diminished mitochondrial membrane potential. No differences in activity were observed for all compounds except , which was slightly less active. Electrochemical analyses revealed for all compounds a fast attachment of the solvent dimethyl sulfoxide and a release of the axial ligand A. In contrast, in dichloromethane and acetonitrile, ligand exchange did not take place, as analyzed by measurements of the standard potential for the iron(III/II) redox reaction.
[-二水杨醛缩-1,2-苯二胺]铁(III)（[salophene]铁(III))衍生物-带有阴离子轴向配体（A=Cl、NO、SCN、CHCOO)和配合物[Fe(salophene)(Im)]ClO4和[Fe(salophene)(MeIm)]ClO4以及中性配体（A=咪唑，1-甲基咪唑）以及μ-氧合二聚体抑制增殖，降低代谢活性，并增加线粒体活性氧。通过抑制剂实验以及脂质过氧化和线粒体膜电位降低的诱导，确定铁死亡是作用机制的一部分。除了[Fe(salophene)(MeIm)]ClO4，所有化合物的活性均无差异，后者活性略低。电化学分析表明，所有化合物都能迅速与溶剂二甲亚砜结合，并释放出轴向配体 A。相比之下，在二氯甲烷和乙腈中，如通过铁(III/II)氧化还原反应标准电势的测量所分析的，配体交换并未发生。
