American Chemical Society
np2c00716_si_001.pdf (4.38 MB)

Purpurascenines A–C, Azepino-Indole Alkaloids from Cortinarius purpurascens: Isolation, Biosynthesis, and Activity Studies on the 5‑HT2A Receptor

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journal contribution
posted on 2023-06-12, 12:03 authored by Yen T. H. Lam, Jana Hoppe, Quang N. Dang, Andrea Porzel, Alena Soboleva, Wolfgang Brandt, Robert Rennert, Hidayat Hussain, Mehdi D. Davari, Ludger Wessjohann, Norbert Arnold
Three previously undescribed azepino-indole alkaloids, named purpurascenines A–C (13), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 13 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet–Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A–C (13). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor’s active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.