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Advances in Bioactivation Research

  • Book
  • © 2008

Overview

Editors:
  1. Adnan Elfarra

    1. School of Pharmacy, University of Wisconsin, Madison, U.S.A.

    View editor publications

    You can also search for this editor in PubMed   Google Scholar

  • Provides researchers with recent information on bioactivation reactions of drugs and toxicants
  • Includes supplementary material: sn.pub/extras

Part of the book series: Biotechnology: Pharmaceutical Aspects (PHARMASP, volume IX)

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Table of contents (17 chapters)

  1. Front Matter

    Pages 1-7
    Download chapter PDF

  2. General Concepts and Basic Mechanisms

    1. Front Matter

      Pages 1-1
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    2. Metabolic Concerns in Drug Design

      • Jeffrey P. Jones
      Pages 1-24

    3. Role of Bioactivation in Idiosyncratic Drug Toxicity: Structure–Toxicity Relationships

      • Amit S. Kalgutkar
      Pages 1-29

    4. Michael Addition–Elimination Reactions: Roles in Toxicity and Potential New Therapeutic Applications

      • Adnan A. Elfarra, Renee J. Krause
      Pages 1-12

    5. Induction of Drug-Metabolizing Enzymes: Contrasting Roles in Detoxification and Bioactivation of Drugs and Xenobiotics

      • Sharon L. Ripp
      Pages 1-34

    6. Mechanism-Based Inactivation of Cytochrome P450 2A and 2B Enzymes

      • Sharon E. Murphy, Linda B. von Weymarn
      Pages 1-29

    7. CYP2E1 – Biochemical and Toxicological Aspects and Role in Alcohol-Induced Liver Injury

      • Arthur I. Cederbaum
      Pages 1-36

    8. One- and Two-Electron-Mediated Reduction of Quinones: Enzymology and Toxicological Implications

      • David Siegel, Phillip Reigan, David Ross
      Pages 1-29

    9. Lipoxidation-Derived Electrophiles as Biological Reactive Intermediates

      • De Lin, Lawrence M. Sayre
      Pages 1-34

    10. Bioactivation and Protein Modification Reactions of Unsaturated Aldehydes

      • J. Cai, B.G. Hill, A. Bhatnagar, W.M. Pierce Jr, R.A. Prough
      Pages 1-21

  3. Tissue-Specific Features and Risk Assessment Applications

    1. Front Matter

      Pages 1-1
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    2. Adaptive Responses and Signal Transduction Pathways in Chemically Induced Mitochondrial Dysfunction and Cell Death

      • Lawrence H. Lash
      Pages 1-33

    3. Hepatic Bioactivation and Drug-Induced Liver Injury

      • Raymond A. Kemper, George Lai
      Pages 1-33

    4. Role of Cysteine S-Conjugate β-Lyases in the Bioactivation of Renal Toxicants

      • Arthur J. L. Cooper, John T. Pinto
      Pages 1-24

    5. Bioactivation of Xenobiotics in Lung: Role of CYPs and FMOs

      • David E. Williams
      Pages 1-27

    6. Generation of Reactive Metabolites and Associated DNA Adducts from Benzene, Butadiene, and PAH in Bone Marrow. Their Effects on Hematopoiesis and Impact on Human Health

      • Colin Jefcoate, Michele Larsen
      Pages 1-34

    7. Butadiene-Mediated Mutagenesis and Carcinogenesis

      • Jonathan B. Ward, Jeffrey K. Wickliffe, Michael P. Stone, Thomas M. Harris, Priscilla H. Fernandes, R. Stephen Lloyd
      Pages 1-31

    8. Pharmacogenetics of Drug Bioactivation Pathways

      • Lauren A. Trepanier
      Pages 1-20

    9. Human Phenanthrene Metabolites as Probes for the Metabolic Activation and Detoxification of Carcinogenic Polycyclic Aromatic Hydrocarbons

      • Stephen S. Hecht
      Pages 1-22
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Keywords

About this book

I have always been interested in chemistry and biology. My undergraduate, graduate, and postdoctoral trainings in pharmacy, medicinal chemistry and pharmacology, respectively, have strengthened this interest and led me to realize that significant advances in medicine have frequently been realized because of research at the chem- try–biology interface. I am hoping that this comprehensive volume on recent advances in bioactivation research will stimulate pharmacologists, medicinal chemists, phar- ceutical scientists, and graduate students in these fields and related areas to consider and use bioactivation research when they explore and chart new frontiers in drug design and drug development and when they consider ways to reduce the side effects of existing drugs by making prodrugs. As for the toxicologists and environmental health scientists, I hope this volume will help them generate the knowledge needed to understand better mechanisms of toxicity to improve human risk assessments and intervention methods after occupational or environmental exposure to various hazardous chemicals. Adnan A. Elfarra, Ph. D. vii Part I General Concepts and Basic Mechanisms 1 Metabolic Concerns in Drug Design Jeffrey P. Jones Department of Chemistry, Washington State University, Pullman, WA 99164, USA e-mail: jpj@wsu. edu Keywords: Cytochrome P450 Aldehyde Oxidase Drug–Drug Interactions Mechanism-based Virtual Screening ADMET Regioselectivity 1. 1. Introduction Due to recent technological innovations, such as genomics, combinatorial chemistry, and high-throughput screening, the identification of disease targets and of compounds that are active against these targets (‘‘leads’’) can now be carried out efficiently.

Editors and Affiliations

  • School of Pharmacy, University of Wisconsin, Madison, U.S.A.

    Adnan Elfarra

About the editor

Dr. Elfarra received his B.S. degree in Pharmacy at Cairo University, Cairo, Egypt, in 1975 and his Ph.D. degree in Medicinal Chemistry at the University of Minnesota, Minneapolis, MN, in 1983. In 1985, Dr. Elfarra joined Shell Development Company in Houston, Texas as an associate research toxicologist after he completed his postdoctoral training in Pharmacology at the University of Rochester in Rochester, NY. Dr. Elfarra joined the University of Wisconsin-Madison as assistant professor in 1986. He was promoted to associate and full professor in 1992 and 1996, respectively. He served as the chair of the campus Biosafety Committee and has trained a large number of undergraduate students, graduate students, and postdoctoral students in his laboratory. He is the current director of the institutional training grant from NIEHS. Dr. Elfarra has served on the executive committee for the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, and has organized and participated in many national and international symposia focused on topics related to his research. He has served as consultant for many organizations, such as NIH, the National Research Council Board on Environmental Studies and Toxicology, the Health Effects Institute, Health Canada, and the International Agency for Research on Cancer.

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