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Investigating the ability of the microbial model Cunninghamella elegans for the metabolism of synthetic tryptamines
Author(s) -
Grafinger Katharina Elisabeth,
Wilke Andreas,
König Stefan,
Weinmann Wolfgang
Publication year - 2019
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2544
Subject(s) - tryptamine , tryptamines , biotransformation , chemistry , metabolism , hydroxylation , in vivo , biochemistry , metabolite , designer drug , metabolic pathway , biology , pharmacology , enzyme , drug , microbiology and biotechnology
Tryptamines can occur naturally in plants, mushrooms, microbes, and amphibians. Synthetic tryptamines are sold as new psychoactive substances (NPS) because of their hallucinogenic effects. When it comes to NPS, metabolism studies are of crucial importance, due to the lack of pharmacological and toxicological data. Different approaches can be taken to study in vitro and in vivo metabolism of xenobiotica. The zygomycete fungus Cunninghamella elegans ( C. elegans ) can be used as a microbial model for the study of drug metabolism. The current study investigated the biotransformation of four naturally occurring and synthetic tryptamines [ N,N‐ Dimethyltryptamine (DMT), 4‐hydroxy‐ N ‐methyl‐ N ‐ethyltryptamine (4‐HO‐MET), N,N ‐di allyl‐5‐methoxy tryptamine (5‐MeO‐DALT) and 5‐methoxy‐ N ‐methyl‐ N ‐isoporpoyltryptamine (5‐MeO‐MiPT)] in C. elegans after incubation for 72 hours. Metabolites were identified using liquid chromatography–high resolution–tandem mass spectrometry (LC–HR–MS/MS) with a quadrupole time‐of‐flight (QqTOF) instrument. Results were compared to already published data on these substances. C. elegans was capable of producing all major biotransformation steps: hydroxylation, N ‐oxide formation, carboxylation, deamination, and demethylation. On average 63% of phase I metabolites found in the literature could also be detected in C. elegans . Additionally, metabolites specific for C. elegans were identified. Therefore, C. elegans is a suitable complementary model to other in vitro or in vivo methods to study the metabolism of naturally occurring or synthetic tryptamines.