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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Molecular toxicology and the medicinal chemist
1Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Switzerland. bernard.testa@ict.unil.ch
Farmaco (Societa Chimica Italiana : 1989)
|July 11, 1998
Summary
Drug metabolism influences drug effects and how the body processes them. This review explores how functionalization and conjugation reactions in drug metabolism can lead to toxic byproducts, impacting drug safety.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Toxicology
Background:
- Drug metabolism significantly impacts pharmacodynamics and pharmacokinetics.
- Understanding drug metabolism is crucial from early drug research stages.
- Medicinal chemists are interested in aspects like prodrug and soft drug design.
Purpose of the Study:
- To review toxication resulting from drug metabolism reactions.
- Focus on functionalization and conjugation reactions.
- Highlight the role of toxophoric groups and macromolecular adducts.
Main Methods:
- Review of literature on drug metabolism and toxicology.
- Analysis of functionalization reactions (oxidation, reduction).
- Analysis of conjugation reactions (e.g., acylglucuronides, Coenzyme A conjugates).
Main Results:
- Functionalization can yield nucleophilic radicals or electrophilic metabolites.
- Conjugation can produce lipophilic residues or adduct-forming metabolites.
- Macromolecular adducts are key endpoints in molecular toxicology.
Conclusions:
- Toxophoric groups are functional moieties involved in toxication.
- Enzyme specificity, biological factors, and repair mechanisms mitigate toxicological risks.
- Despite potential toxication, organisms possess protective mechanisms against drug metabolism risks.
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