Biomaterial Database

Structure-property and structure-activity relationships of phenylferrocene derivatives as androgen receptor antagonists. 2021

Kotaro Ochiai, and Shinya Fujii

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

Ferrocene is a representative organometallic compound having a sandwich structure with high stability and hydrophobicity. In this study, we determined the physicochemical properties of a series of nitro- and cyanophenylferrocenes, and evaluated their biological activity as androgen receptor (AR) antagonists. Ferrocene derivatives exhibited hydrophobicity parameter π values in the range between 2.54 and 3.23, depending on the substituents, indicating that the hydrophobicity of ferrocene is suitable for its application as a hydrophobic core structure of nuclear receptor ligands. The synthesized ferrocene derivatives showed AR-antagonistic activity, and among them, 3-nitrophenylferrocene 14 exhibited the most potent activity with an IC50 value of 0.28 μM. The developed compounds may be candidates for further structural development as AR antagonists. These findings also support the utility of organometallic species as structural options for drug discovery.

UI	MeSH Term	Description	Entries
D011944	Receptors, Androgen	Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.	Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005296	Ferrous Compounds	Inorganic or organic compounds that contain divalent iron.	Compounds, Ferrous
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075163	Metallocenes	Organometallic compounds that generally consist of two cylcopentadiene ANIONS joined in their centers by a metallic cation such as NICKEL; IRON; or TITANIUM.	Ferrocenes
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D059002	Androgen Receptor Antagonists	Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.	Androgen Receptor Antagonist,Antagonist, Androgen Receptor,Antagonists, Androgen Receptor,Receptor Antagonist, Androgen,Receptor Antagonists, Androgen