Drug metabolism for the perplexed medicinal chemist.

Details

Serval ID
serval:BIB_A552215F9E2F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Drug metabolism for the perplexed medicinal chemist.
Journal
Chemistry & Biodiversity
Author(s)
Testa Bernard
ISSN
1612-1880[electronic]
Publication state
Published
Issued date
2009
Volume
6
Number
11
Pages
2055-2070
Language
english
Abstract
Two related and significant issues may elicit perplexity in medicinal chemists and are discussed here. First, a broad presentation of the pharmacological and toxicological consequences of drug metabolism should justify the significance of drug metabolism and serve as an incentive to further study. When comparing the pharmacological activities of a drug and its metabolite(s), a continuum is found which ranges from soft drugs (no active metabolites) to prodrugs (inactive per se, as illustrated here with clopidogrel and prasugrel). Innumerable intermediate cases document drugs whose activity is shared by one or more metabolites, as exemplified with tamoxifen. The toxicological consequences of metabolism at the molecular, macromolecular, and macroscopic levels are manyfold. A brief overview is offered together with a summary of the reactions of toxification and detoxification of the antiepileptic valproic acid. The second issue discussed in the review is a comparison of the relative significance of cytochromes P450 and other oxidoreductases (EC 1), hydrolases (EC 3), and transferases (EC 2) in drug metabolism, based on a 'guesstimate' of the number of drug metabolites that are known to be produced by them. The conclusion is that oxidoreductases are the main enzymes responsible for the formation of toxic or active metabolites, whereas transferases play the major role in producing inactive and nontoxic metabolites.
Keywords
Valproic Acid, Active Metabolite, In-Vitro, (E)-2-Propyl-2,4-Pentadienoic Acid, Toxic Metabolite, Breast-Cancer, Biochemistry, Discovery, Clopidogrel, Prasugrel
Pubmed
Web of science
Create date
21/12/2009 15:55
Last modification date
20/08/2019 15:10
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