Biomaterial Database

Quantitative structure-activity relationships/comparative molecular field analysis (QSAR/CoMFA) for receptor-binding properties of halogenated estradiol derivatives. 1994

T G Gantchev, and H Ali, and J E van Lier

MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

The 3-D quantitative structure-activity relationships/comparative molecular field analysis (QSAR/CoMFA) paradigm, which considers the primary importance of the molecular fields in biological recognition, is now widely used to analyze and predict receptor-binding properties of various ligands. CoMFA was applied to build 3-D QSAR models of substituted estradiol-receptor interactions, employing 3-D molecular databases of more than 40 molecules. Ligands included the 17 alpha-ethynyl- and isomeric 17 alpha (20E/Z)-(iodovinyl)estradiols and their 7 alpha-, 11 beta-, and 12 beta-methyl (-methoxy) and -ethyl (-ethoxy) derivatives as well as selected 2- and 4-halogenated analogs. The influence of different CoMFA descriptors was studied in order to achieve the highest possible cross-validated r2, as derived from partial least-squares calculations. Special emphasis was put on the analysis of the nature of H-bonding (donor/acceptor) interactions. The model with the best predictive performance (r2 = 0.895) was used to visualize steric and electrostatic features of the QSAR (standard deviation*coefficient contour maps) and to predict receptor-binding affinities (RBA) of substituted estradiols other than those included in the original database. Twenty-seven test molecules were selected, including five which had previously been reported by other investigators. For the latter, a very good correlation with literature RBA values was obtained, which together with the high cross-validated r2 provides evidence for the high predictive capacity of the model. Among the unknown structures, the model suggests several new substitutions to derive at reasonable affinity ligands for the estrogen receptor.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008968	Molecular Conformation	The characteristic three-dimensional shape of a molecule.	Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D011959	Receptors, Estradiol	Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription.	Estradiol Receptors,Estradiol Receptor,Receptor, Estradiol
D004958	Estradiol	The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.	17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D006219	Halogens	A family of nonmetallic, generally electronegative, elements that form group 17 (formerly group VIIa) of the periodic table.	Halogen,Group 17 Elements,Elements, Group 17
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