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Designing Safer (Soft) Drugs by Avoiding the Formation of Toxic and Oxidative Metabolites

  • Nicholas Bodor
  • Peter Buchwald
Part of the Methods in Molecular Biology™ book series (MIMB, volume 186)

Abstract

Living organisms possess not only fine-tuned metabolic mechanisms for endogenous chemicals but also several defensive mechanisms to detoxify xenobiotics. Most metabolic processes that eliminate invading foreign chemicals by transforming them into more hydrophilic or more easily conjugated compounds are oxidative in nature. Unfortunately, many of these mechanisms are indiscriminate, and detoxifying enzymes, such as cytochrome P450 or N-acetyltransferase, can generate toxic reactive intermediates such as epoxides or radicals from otherwise nontoxic compounds (1,2). Chemicals and xenobiotics, therefore, are not always metabolized only into more hydrophilic and less toxic substances, but also into highly reactive chemical species, which then can react with various macromolecules and cause tissue damage or elicit antigen production.

Keywords

Inactive Metabolite Oxidative Metabolite Soft Chemical Nontoxic Compound Carboxylic Ester Hydrolase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Nicholas Bodor
    • 1
  • Peter Buchwald
    • 1
  1. 1.Department of Pharmaceutics, Center for Drug DiscoveryUniversity of Florida, College of PharmacyGainesville

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