Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

International Journal of Molecular Sciences

Mihai V. Putz²  Cosmin Ionaᗼu¹  Ana-Maria Putz¹ 

[1] “Nicolas Georgescu-Roegen” Forming and Research Center of West University of Timişoara, 4th, Oituz Street, Timişoara, RO-300086, Romania; E-Mail:;Laboratory of Computational and Structural Physical Chemistry, Chemistry Department, West University of Timişoara, Pestalozzi Street No.16, Timişoara, RO-300115, Romania; E-Mail:

关键词: genotoxic carcinogenesis;    structural alerts;    OECD principles;    residual-QSAR;    electronegativity and chemical hardness reactivity principles;   

DOI  :  10.3390/ijms12085098

来源: mdpi

【 摘 要 】

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/TD₅₀], i.e., . 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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.