The Biological Target Potential of Organometallic Steroids Chapitre d’ouvrage - 2014

Gérard Jaouen, Siden Top, Michael J. Mcglinchey

Gérard Jaouen, Siden Top, Michael J. Mcglinchey, « The Biological Target Potential of Organometallic Steroids  », in Jaouen, Gérard and Salmain, Michèle (ed.), Bioorganometallic Chemistry, 2014, pp. 43—84. ISBN 978-3-527-67343-8


The discovery of the superfamily of nuclear receptors, represented first by the estrogen receptor (ERα) identified by E.V. Jensen in 1958, caused a veritable revolution in biology. Its repercussions are still with us, in the chemistry of steroids, synthetic selective steroid receptor modulators, and endocrine disruptors. These small molecules, including the group of steroids we will focus on here, can be linked to major diseases (e.g., cancers, osteoporosis, and diabetes), as well as issues relating to fertility and conception, birth control, and environmental diseases. After a brief description of the mechanism of action of the nuclear receptors we will address the issue of the organometallic versions of molecules that can potentially target these receptors, as well as their biological advantages. We have shown via radioactive labeling that certain organometallic hormone complexes have good targeting ability for nuclear receptors. The reversible binding of these complexes with specific receptors as well as the case of irreversible inhibition of estrogen receptors that can sometimes be obtained using carefully selected organometallic moieties will be discussed in this chapter. This work introduces the approach using SERMs, SARMs, and so on, which due to their large numbers are only touched on here. A section gives more complete details of organometallic radiopharmaceuticals, mostly steroidal. In broader strokes the current renaissance underway in the area of organometallic steroids is discussed with emphasis on biological aspects where known. Finally, some directions are indicated concerning new organometallic bioprobes obtained with SERMs and other endocrine disruptors that make new types of analysis possible. This combined with endocrine modulators possessing an additional organometallic function, for example of the redox type, points to a future that looks to be rich in promise.

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