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Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis
Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations A(SA) of electrophilic molecular structures...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179155/ https://www.ncbi.nlm.nih.gov/pubmed/21954348 http://dx.doi.org/10.3390/ijms12085098 |
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author | Putz, Mihai V. Ionaşcu, Cosmin Putz, Ana-Maria Ostafe, Vasile |
author_facet | Putz, Mihai V. Ionaşcu, Cosmin Putz, Ana-Maria Ostafe, Vasile |
author_sort | Putz, Mihai V. |
collection | PubMed |
description | Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations A(SA) of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD(50)], i.e., [Formula: see text]). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., [Formula: see text]. We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles. |
format | Online Article Text |
id | pubmed-3179155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-31791552011-09-27 Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis Putz, Mihai V. Ionaşcu, Cosmin Putz, Ana-Maria Ostafe, Vasile Int J Mol Sci Article Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations A(SA) of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD(50)], i.e., [Formula: see text]). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., [Formula: see text]. We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles. Molecular Diversity Preservation International (MDPI) 2011-08-11 /pmc/articles/PMC3179155/ /pubmed/21954348 http://dx.doi.org/10.3390/ijms12085098 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Putz, Mihai V. Ionaşcu, Cosmin Putz, Ana-Maria Ostafe, Vasile Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title | Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title_full | Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title_fullStr | Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title_full_unstemmed | Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title_short | Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis |
title_sort | alert-qsar. implications for electrophilic theory of chemical carcinogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179155/ https://www.ncbi.nlm.nih.gov/pubmed/21954348 http://dx.doi.org/10.3390/ijms12085098 |
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