Skip to Main content Skip to Navigation
Journal articles

Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites

Abstract : Ferrociphenols have been found to have high antiproliferative activity against estrogen-independent breast cancer cells. The rat and human liver microsome-mediated metabolism of three compounds of the ferrocifen (FC) family, 1,1-bis(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene (FC1), 1-(4-hydroxyphenyl)-1-(phenyl)-2-ferrocenyl-but-1-ene (FC2), and 1-[4-(3-dimethylaminopropoxy)phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl- but-1-ene (FC3), was studied. Three main metabolite classes were identified: quinone methides (QMs) deriving from two-electron oxidation of FCs, cyclic indene products (CPs) deriving from acid-catalyzed cyclization of QMs, and allylic alcohols (AAs) deriving from hydroxylation of FCs. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N-benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450-dependent oxidation of the phenol function and hydroxylation of the allylic CH2 group of FCs leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA-MB-231 hormone-independent breast cancer cells.
Complete list of metadata

Cited literature [26 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-01230370
Contributor : Gestionnaire Hal-Upmc Connect in order to contact the contributor
Submitted on : Saturday, May 12, 2018 - 3:48:12 PM
Last modification on : Thursday, December 9, 2021 - 11:20:02 AM
Long-term archiving on: : Monday, September 24, 2018 - 6:06:09 PM

Files

pub-1040.pdf
Files produced by the author(s)

Identifiers

Citation

Marie-Aude Richard, Didier Hamels, Pascal Pigeon, Siden Top, Patrick M. Dansette, et al.. Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites. ChemMedChem, Wiley-VCH Verlag, 2015, 10 (6), pp.981-990. ⟨10.1002/cmdc.201500075⟩. ⟨hal-01230370⟩

Share

Metrics

Les métriques sont temporairement indisponibles