Cell-specific effects of methoxy-substituted iron(III) salophene complexes
Astrid Dagmar Bernkop-Schnürch1, Martin Hermann2, Sophie Luise Strich3
1Department of Pharmaceutical Chemistry, Institute of Pharmacy, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
Bioorganic Chemistry
|July 25, 2026
Summary
Iron(III) complexes C1, C3, and C4 show rapid, cell-specific mitochondrial effects and cytotoxicity in cancer cells within 24 hours. Complex C2 is inactive despite cellular uptake.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Iron(III) complexes with N,N'-Bis(salicylidene)-1,2-phenylenediamine ligands (C1-C4) exhibit cytotoxic activity.
- Previous studies indicated maximum cytotoxicity at 48 hours, prompting investigation into earlier cellular events.
Purpose of the Study:
- To investigate the early cellular and mitochondrial effects of iron(III) complexes C1-C4 after 24 hours of incubation.
- To determine cell type-specific responses in breast cancer (MDA-MB 231), leukemia (HL-60), and normal epithelial (MCF-10A) cells.
Main Methods:
- Cell-based assays and mitochondria-related assays were employed.
- Cellular uptake, mitochondrial membrane potential, reactive oxygen species (ROS) production, and oxygen consumption were measured.
- Apoptosis and necrosis were assessed after 24-hour incubation.
Main Results:
- Complexes C1, C3, and C4 were rapidly taken up by MDA-MB 231 and HL-60 cells.
- C1, C3, and C4 induced distinct mitochondrial responses (depolarization, ROS increase, respiration impairment) in a cell-dependent manner.
- C2 showed minimal activity despite efficient uptake, while C1, C3, and C4 caused cell death in cancer cells but spared normal cells.
Conclusions:
- Iron(III) complexes C1, C3, and C4 trigger rapid, cell-specific mitochondrial dysfunction contributing to early cytotoxicity.
- The 4-methoxy substituted complex C2 is ineffective, highlighting the importance of substituent position.
- These findings provide insights into the early mechanisms of action for potential anticancer agents.
Keywords:
Cell deathCellular respirationIron(III) salophene complexesMitochondrial membrane potentialReactive oxygen speciesMore Related Videos
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