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- Title
Cunninghamella as a Microbiological Model for Metabolism of Histamine H Receptor Antagonist 1-[3-(4- tert-Butylphenoxy)propyl]piperidine.
- Authors
Pękala, Elżbieta; Kubowicz, Paulina; Łażewska, Dorota
- Abstract
The aim of the study was to analyze the ability of the microorganism Cunninghamella to carry out the biotransformation of 1-[3-(4- tert-butylphenoxy)propyl]piperidine (DL76) and to compare the obtained results with in silico models. Biotransformation was carried out by three strains of filamentous fungus: Cunninghamella echinulata, Cunninghamella blakesleeana, and Cunninghamella elegans. Most probable direction of DL76 metabolic transition was the oxidation of the methyl group in the tert-butyl moiety leading to the formation of the metabolite with I° alcohol properties. This kind of reaction was conducted by all three strains tested. However, only in the case of C. blakesleeana that biotransformation product had a structure of carboxylic acid. CYP2C19 was identified by Metasite software to be the isoform of major importance in the oxidation process in the tert-butyl moiety of DL76. In silico data coincide with the results of experiments conducted in vitro. It was confirmed that Cunninghamella fungi are a very good model to study the metabolism of xenobiotics. The computational methods and microbial models of metabolism can be used as useful tools in early ADME-Tox assays in the process of developing new drug candidates.
- Subjects
METABOLISM; HISTAMINE; ANTAGONISTIC fungi; PIPERIDINE; BIOTRANSFORMATION (Metabolism)
- Publication
Applied Biochemistry & Biotechnology, 2012, Vol 168, Issue 6, p1584
- ISSN
0273-2289
- Publication type
Academic Journal
- DOI
10.1007/s12010-012-9880-8