Purpurascenines A-C, Azepino-Indole Alkaloids from : Isolation, Biosynthesis, and Activity Studies on the 5-HT 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 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.