Abstract
Seongsanamide A is a bicyclic peptide with an isodityrosine residue discovered in Bacillus safensis 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.
Highlights
Several bicyclic peptide compounds have been reported from marine sponges [3,4], microorganisms [5], and mushrooms [6], which are used as antifungal agents, an HDAC
To choose the optimum polarity mode, standard solutions of seongsanamide A were infused into the MS and analyzed in positive and negative ionization modes using an infused into the MS and analyzed in positive and negative ionization modes using an electrospray ionization source
The results showed that the chromatographic peaks in the electrospray ionization source
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Bicyclic peptides exhibit higher conformational rigidity, metabolic stability, and membrane permeability compared with linear or monocyclic peptides. They are considered potential leads for the drug discovery stage [1,2]. The increased conformational rigidity of bicyclic peptides further improves their binding affinity to various drug targets and enhances target selectivity [1]. Several bicyclic peptide compounds have been reported from marine sponges (theonellamides) [3,4], microorganisms (thailandepsin B) [5], and mushrooms (amatoxin and phallotoxin) [6], which are used as antifungal agents, an HDAC inhibitor, and RNA polymerase inhibitors, respectively
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
