Purpurascenines A-C, Azepino-Indole Alkaloids from Cortinarius purpurascens : Isolation, Biosynthesis, and Activity Studies on the 5-HT 2A Receptor

Three previously undescribed azepino-indole alkaloids, named purpurascenines A-C ( - ), together with the new-to-nature 7-hydroxytryptophan ( ) as well as two known compounds, adenosine ( ) and riboflavin ( ), were isolated from fruiting bodies of Fr. (Cortinariaceae). The structures of - were eluci...

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Published in:Journal of natural products (Washington, D.C.) D.C.), 2023-06, Vol.86 (6), p.1373-1384
Main Authors: Lam, Yen T H, Hoppe, Jana, Dang, Quang N, Porzel, Andrea, Soboleva, Alena, Brandt, Wolfgang, Rennert, Robert, Hussain, Hidayat, Davari, Mehdi D, Wessjohann, Ludger, Arnold, Norbert
Format: Article
Language:English
Subjects:
Cortinarius - chemistry
Cortinarius - metabolism
Humans
Indole Alkaloids - pharmacology
Male
Receptor, Serotonin, 5-HT2A
Serotonin - metabolism
Serotonin - pharmacology
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Summary:Three previously undescribed azepino-indole alkaloids, named purpurascenines A-C ( - ), together with the new-to-nature 7-hydroxytryptophan ( ) as well as two known compounds, adenosine ( ) and riboflavin ( ), were isolated from fruiting bodies of Fr. (Cortinariaceae). The structures of - were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A ( ) was investigated by experiments using C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of . The incorporation of C into was analyzed using 1D NMR and HRESIMS methods. With [3- C]-pyruvate, a dramatic enrichment of C was observed, and hence a biosynthetic route via a direct Pictet-Spengler reaction between α-keto acids and 7-hydroxytryptophan ( ) is suggested for the biosynthesis of purpurascenines A-C ( - ). Compound exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An docking study confirmed the hypothesis that purpurascenine A ( ) could bind to the 5-HT serotonin receptor's active site. A new functional 5-HT receptor activation assay showed no functional agonistic but some antagonistic effects of against the 5-HT-dependent 5-HT activation and likely antagonistic effects on putative constitutive activity of the 5-HT receptor.
ISSN:0163-3864
1520-6025
DOI:10.1021/acs.jnatprod.2c00716