Current Computer Aided-Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


The Role of Hydrophobicity in Toxicity Prediction

Author(s): Mark T. D. Cronin

Affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England,UK.


The influence of hydrophobicity on toxic potency has been known for over a century. This paper summarises some of the key areas where hydrophobicity, in the form of the logarithm of the octanol-water partition coefficient (log P), is incorporated into quantitative structure-activity relationships (QSARs) for toxicity. Log P is frequently seen in QSARs for acute aquatic toxicity, especially for chemicals acting by non-reactive (i.e. in the absence of covalent binding) mechanisms of action.Within the narcoticmode of acute toxicity, a number of QSARs based on log P have been derived for different mechanisms such as non-polar and polar narcoses. For reactive chemicals, hydrophobicity is important for transport and distribution, such that hydrophobicity based QSARs may be derived for covalently binding chemicals with “constant” reactivity. Due to its contribution to pharmacokinetics, log P is also found in models for other mammalian toxicities such carcinogenicity and skin sensitisation.

Keywords: Toxicity, hydrophobicity, lipophilicity, quantitative structure-activity relationship, QSAR, n-octanol-water partition coefficient, narcosis, environmental effects, reactive toxicity, skin sensitisation

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Article Details

Page: [405 - 413]
Pages: 9
DOI: 10.2174/157340906778992346
Price: $58