Identification of parthenolide metabolites in human liver microsomes by LC-Q-TOF-MS/MS.

Sesquiterpene lactones (SLs) are highly active specialized metabolites, bearing an α-methylene-γ-lactone ring which is reacting through Michael type additions with sulfhydryl groups in biological systems. Parthenolide is a natural SL isolated from Tanacetum parthenium L. which has a long-term use in folk medicine, while due to its anti-cancer potential its semi-synthetic derivative was subject of clinical trials [1]. Although there are some data on the metabolic pathways and metabolites of a few SLs [2], parthenolide has not yet been investigated, thus this study characterizes its metabolites in human liver microsomes. Phase I, phase II (glucuronidation) as well as combined phase I+II metabolism were studied (Fig. 1). Metabolites were identified via liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry. Eight metabolites were found, including four methylated (one lost the double bond at Δ _10-1) and one hydroxylated. Moreover, no metabolites with an opened lactone-ring could be identified, however the exomethylenic double bond at Δ _11-13 was subject of reduction, oxidation or glucuronidation.

Publikationsverlauf

Artikel online veröffentlicht:
13. Dezember 2021

• References

• 1 Moujir et al 2020. Appl Sci, 10, 3001.
• 2 Yu et al 2020. Drug Metab Rev, 53, 122-140.