caa a22 4500 378861484 CHVBK 20180305123347.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375112363 doi (NATIONALLICENCE)gruyter-10.1351/pac200375112363 Mechanism-based QSAR approach to the study of the toxicity of endocrine active substances [Elektronische Daten] [C. D. Selassie, R. Garg, S. Mekapati] 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. © 2013 Walter de Gruyter GmbH, Berlin/Boston Selassie C. D. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut Garg R. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut Mekapati S. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2363-2373 0033-4545 75:11-12<2363 2003 75 pac https://doi.org/10.1351/pac200375112363 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375112363 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Selassie C. D. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut NATIONALLICENCE 700 1- Garg R. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut NATIONALLICENCE 700 1- Mekapati S. Chemistry Department, Pomona College, Claremont, CA 91711, USA aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2363-2373 0033-4545 75:11-12<2363 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter