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Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone‐Receptor Affinity of Several Organometallic Groups at the 17 α Position
Author(s) -
Top Siden,
El Hafa Hassane,
Vessières Anne,
Huché Michel,
Vaissermann Jacqueline,
Jaouen Gérard
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m
Subject(s) - substituent , moiety , chemistry , stereochemistry , group 2 organometallic chemistry , ligand (biochemistry) , alkyne , estrogen receptor , receptor , molecule , organic chemistry , catalysis , biochemistry , medicine , cancer , breast cancer
In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17 α position, modification of 17 β ‐estradiol at this position was carried out by using the organometallic groups ‐CC‐( η 5 ‐C 5 H 4 )RuCp, CH 2 ‐( η 5 ‐C 5 H 4 )RuCp, ‐CC‐( η 5 ‐C 5 H 4 )W(CO) 3 (Me), ‐(CCCHO)Co 2 (CO) 6 , and ‐(CCCH 2 OH)Co 2 (CO) 6 . The relative binding affinity ( RBA ) values for estradiol receptor alpha showed that recognition was good ( RBA between 20 and 13.5 %) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced ( RBA =1 %) for a substituent such as ‐CH 2 ‐( η 5 ‐C 5 H 4 )RuCp, in which the spacer is reduced to a single flexible sp 3 carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular‐modeling study in which 5 , an organometallic hormone with a rigid spacer, or 7 , a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand‐Binding Domain of estrogen receptor alpha.