Abstract
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
Current Computer-Aided Drug Design
Title: The Role of Hydrophobicity in Toxicity Prediction
Volume: 2 Issue: 4
Author(s): Mark T. D. Cronin
Affiliation:
Keywords: Toxicity, hydrophobicity, lipophilicity, quantitative structure-activity relationship, QSAR, n-octanol-water partition coefficient, narcosis, environmental effects, reactive toxicity, skin sensitisation
Abstract: 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.
Export Options
About this article
Cite this article as:
D. Cronin T. Mark, The Role of Hydrophobicity in Toxicity Prediction, Current Computer-Aided Drug Design 2006; 2 (4) . https://dx.doi.org/10.2174/157340906778992346
DOI https://dx.doi.org/10.2174/157340906778992346 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Editorial [ Pathophysiological Basis For New Frontiers in Arterial Hypertension Guest Editor: A. Nitenberg ]
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Impact of Knowledge, Attitude and Practice on the Management of Type 2 Diabetes Mellitus in Developing Countries: A Review
Current Diabetes Reviews KRAS: A Promising Therapeutic Target for Cancer Treatment
Current Topics in Medicinal Chemistry Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy
Current Drug Targets Impact of Cytochrome P450 2C19*2 and *3 on Clopidogrel Loading Dose in Saudi Patients with Acute Coronary Syndrome
Drug Metabolism Letters Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets An Overview of Modern Extraction Techniques for the Determination of Organic Pollutants in Environmental Matrices: A Review
Current Organic Chemistry Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus
Current Diabetes Reviews The Mitochondrial Free Radical Theory of Aging: A Critical View
Current Aging Science Regulation of GLUT4 Transcription and Gene Expression
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Lipoic Acid: A Novel Therapeutic Approach for Multiple Sclerosis and Other Chronic Inflammatory Diseases of the CNS
Endocrine, Metabolic & Immune Disorders - Drug Targets Regulation of Apolipoprotein B by Natural Products and Nutraceuticals: A Comprehensive Review
Current Medicinal Chemistry Sodium-Glucose Cotransporter Inhibitors in Non- Diabetic Heart Failure: A Narrative Review
Cardiovascular & Hematological Disorders-Drug Targets Circulating MicroRNAs and Blood-Brain-Barrier Function in Breast Cancer Metastasis
Current Pharmaceutical Design A Review on Biological Activities and Chemical Synthesis of Hydrazide Derivatives
Current Medicinal Chemistry Role of Central and Peripheral Chemoreceptors in Vasopressin Secretion Control
Endocrine, Metabolic & Immune Disorders - Drug Targets A Medicinal Mushroom: Phellinus Linteus
Current Medicinal Chemistry Patent Selections
Recent Patents on Mechanical Engineering Structural Basis for the Design of PPAR-γ Ligands: A Survey on Quantitative Structure- Activity Relationships
Mini-Reviews in Medicinal Chemistry Stem Cell Therapies for Ischemic Cardiovascular Diseases
Recent Patents on Regenerative Medicine