Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells

Laura Cunningham; Yong Wang; Chris Nottingham; Jammah Pagsulingan; Gérard Jaouen; Michael J. McGlinchey; Patrick J. Guiry

doi:10.1002/cbic.202000311

Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells

Laura Cunningham, Yong Wang, Chris Nottingham, Jammah Pagsulingan, Gérard Jaouen, Michael J. McGlinchey, Patrick J. Guiry

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

9 Citations (Scopus)

Abstract

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 Ag₂O 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.

Original language	English
Pages (from-to)	2974-2981
Number of pages	8
Journal	ChemBioChem
Volume	21
Issue number	20
DOIs	https://doi.org/10.1002/cbic.202000311
Publication status	Published - 15 Oct 2020
Externally published	Yes

Keywords

anti-tumor agents
bio-organometallics
chirality
enantioselective synthesis
ferrocifen

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cbic.202000311

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title = "Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells",

abstract = "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 Ag2O 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.",

keywords = "anti-tumor agents, bio-organometallics, chirality, enantioselective synthesis, ferrocifen",

author = "Laura Cunningham and Yong Wang and Chris Nottingham and Jammah Pagsulingan and G{\'e}rard Jaouen and McGlinchey, {Michael J.} and Guiry, {Patrick J.}",

note = "Publisher Copyright: {\textcopyright} 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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month = oct,

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doi = "10.1002/cbic.202000311",

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AU - Cunningham, Laura

AU - Wang, Yong

AU - Nottingham, Chris

AU - Pagsulingan, Jammah

AU - Jaouen, Gérard

AU - McGlinchey, Michael J.

AU - Guiry, Patrick J.

PY - 2020/10/15

Y1 - 2020/10/15

N2 - 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 Ag2O 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.

AB - 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 Ag2O 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.

KW - anti-tumor agents

KW - bio-organometallics

KW - chirality

KW - enantioselective synthesis

KW - ferrocifen

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JO - ChemBioChem

JF - ChemBioChem

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Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells

Abstract

Keywords

UN SDGs

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