In Vitro Metabolism Study of Seongsanamide A in Human Liver Microsomes Using Non-Targeted Metabolomics and Feature-Based Molecular Networking

• Main Authors: Zhexue Wu (Author), Geum Jin Kim (Author), So-Young Park (Author), Jong Cheol Shon (Author), Kwang-Hyeon Liu (Author), Hyukjae Choi (Author)
• Format: Book
• Published: MDPI AG, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Seongsanamide A is a bicyclic peptide with an isodityrosine residue discovered in <i>Bacillus safensis</i> KCTC 12796BP which exhibits anti-allergic activity in vitro and in vivo without significant cytotoxicity. The purpose of this study was to elucidate the in vitro metabolic pathway and potential for drug interactions of seongsanamide A in human liver microsomes using non-targeted metabolomics and feature-based molecular networking (FBMN) techniques. We identified four metabolites, and their structures were elucidated by interpretation of high-resolution tandem mass spectra. The primary metabolic pathway associated with seongsanamide A metabolism was hydroxylation and oxidative hydrolysis. A reaction phenotyping study was also performed using recombinant cytochrome P450 isoforms. CYP3A4 and CYP3A5 were identified as the major metabolic enzymes responsible for metabolite formation. Seongsanamide A did not inhibit the cytochrome P450 isoforms commonly involved in drug metabolism (IC₅₀ > 10 µM). These results will contribute to further understanding the metabolism and drug interaction potential of various bicyclic peptides.

Item Description

10.3390/pharmaceutics13071031
1999-4923