In:
ChemMedChem, Wiley, Vol. 14, No. 19 ( 2019-10-04), p. 1717-1726
Abstract:
The ferrocenyl diphenol complexes 1,1‐bis(4′‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( 1 ) and 1,2‐bis(4′‐hydroxyphenyl)‐1‐ferrocenyl‐but‐1‐ene [( Z )‐ 2 ], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells ( 1 is far more cytotoxic than 2 ). In this study, our goal was to discover the origin of this difference by comparing their reactivity and biological behaviour. In terms of common behaviour, we found that 1 and 2 are both efficient inhibitors of thioredoxin reductase (TrxR) in vitro after oxidation by a horseradish peroxidase/H 2 O 2 system. However, as 1 is only a moderate inhibitor of TrxR in MDA‐MB‐231 cells, TrxR is probably not the major target responsible for the cytotoxicity of 1 . In terms of differences, we noted that 1 induced a significant redox imbalance characterised by lipid peroxidation and thiol oxidation, and a moderate decrease of the mitochondrial membrane potential in breast cancer cells, whereas 2 has almost no effect. These results underline the importance of the trans configuration in the ferrocenyl–double bond–phenol motif, which is present in 1 but is cis in ( Z )‐ 2 .
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201900430
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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