Mechanism-based QSAR approach to the study of the toxicity of endocrine active substances

Autor:	Cynthia Dias Selassie, Suresh Babu Mekapati, Rajni Garg
Rok vydání:	2003
Předmět:	Steric effects Quantitative structure–activity relationship Chemistry Stereochemistry General Chemical Engineering Electronic effect Mechanism based Estrogen receptor Aromaticity General Chemistry Receptor Binding affinities
Zdroj:	Pure and Applied Chemistry. 75:2363-2373
ISSN:	1365-3075 0033-4545
DOI:	10.1351/pac200375112363
Popis:	Mechanism-based QSAR models for interactions between various ligands and the estrogenic receptor are developed by using well-developed physicochemical parameters. Common features of these QSARs are identified, and deficiencies in some datasets are highlighted. The relative binding affinities of various substituted hexestrols to estrogen receptors are examined in terms of their steric, electronic, and hydrophobic attributes. Different QSARs for hexestrols and tamoxifens reveal that steric effects are of overriding importance in variations of binding affinity. In the few cases where a large number of diverse substituents are located on aromatic rings, electronic effects emerge and suggest that electron-donating groups enhance binding to the receptor while hydrophobicity plays a marginal role in decreasing binding affinity. With substituted phenols bearing alkyl-type substituents and substituted hydroxy-biphenyls, the binding is strictly dependent on hydrophobicity and size. These QSAR models are described in detail and examined together to illustrate the utility of lateral validation in mechanistic interpretation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ce38a803c69e7dd2a474edd7de8615d1 https://doi.org/10.1351/pac200375112363 Zobrazit plný text záznamu