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Chemical metabolite synthesis and profiling: Mimicking in vivo biotransformation reactions.

Authors :
Chhatrapati Bisen A
Nashik Sanap S
Agrawal S
Biswas A
Sankar Bhatta R
Source :
Bioorganic chemistry [Bioorg Chem] 2023 Oct; Vol. 139, pp. 106722. Date of Electronic Publication: 2023 Jul 08.
Publication Year :
2023

Abstract

Biotransformation was previously viewed as merely the structural characterization of drug metabolites, and it was performed only when drug candidates entered clinical development. The synthesis of drug metabolites is crucial to the drug development process because it generates either pharmacologically active, inactive, or reactive molecules and hence their characterization and comprehensive pharmacological evaluation is necessary. The chemical metabolite synthesis is very challenging due to the complex structures of many drug molecules, presence of multiple stereocenters, poor reaction yields, and the formation of unwanted by-products. Drug metabolites and their chemical synthesis have immense significance in the drug discovery process. The chemical synthesis of metabolites facilitates on- or off-target pharmacological and toxicological evaluations at the easiest. In a broader view metabolite could be a target lead molecule for drug design, toxic reactive metabolites, pharmaceutical standards for bioanalytical methods, etc. Collectively these metabolite information dossiers will aid regulatory agencies such as the EMA and FDA in maintaining strict vigilance over drug manufacturers with regard to the safety of NCE's and their hidden metabolites. Herein, we are presenting a systematic compilation of chemical and biocatalytic strategies reported to date for pharmaceutical drug metabolite synthesis. This review report is very useful for the laboratory synthesis of new drug metabolites, and their preclinical biological evaluation could aid in the detection of early threats (alerts) in drug discovery, eliminate the toxicity profile, explore newer pharmacology, and delivering a promising and safe drug candidate to humankind.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023. Published by Elsevier Inc.)

Details

Language :
English
ISSN :
1090-2120
Volume :
139
Database :
MEDLINE
Journal :
Bioorganic chemistry
Publication Type :
Academic Journal
Accession number :
37453238
Full Text :
https://doi.org/10.1016/j.bioorg.2023.106722