title: Cunninghamella as a microbiological model for metabolism of histamine H(3) receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine.
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.
authors.affiliation: Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland. elzbieta.pekala@uj.edu.pl
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
authors.forename: Paulina
authors.initials: P
authors.lastname: Kubowicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Łażewska
mesh_terms: D001711:Biotransformation; D020093:Cunninghamella / Q000737:chemistry / Q000378:metabolism*; D006633:Histamine Antagonists / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*
chemical_list: C533358:1-(3-(4-tert-butylphenoxy)propyl)-4-piperidino-piperidine; D006633:Histamine Antagonists; D010880:Piperidines