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Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells
Author(s) -
Cunningham Laura,
Wang Yong,
Nottingham Chris,
Pagsulingan Jammah,
Jaouen Gérard,
McGlinchey Michael J.,
Guiry Patrick J.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000311
Subject(s) - enantioselective synthesis , quinone methide , tamoxifen , enantiomer , intramolecular force , chemistry , stereochemistry , cancer cell , combinatorial chemistry , breast cancer , quinone , catalysis , biochemistry , cancer , medicine
The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium‐catalysed intramolecular direct C−H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag 2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB‐231 cell lines. This bioactivity arises from two mechanisms: Fenton‐type chemistry and the anti‐estrogenic activity associated with the tamoxifen‐like structure.