Purpurascenines A–C, Azepino-Indole Alkaloids from Cortinarius purpurascens: Isolation, Biosynthesis, and Activity Studies on the 5-HT2AReceptor

Three previously undescribed azepino-indole alkaloids, named purpurascenines A–C (1–3), 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 purpurascensFr. (Cortinariaceae). The structures of 1–3were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivoexperiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1was 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 (1–3). Compound 1exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silicodocking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2Aserotonin receptor’s active site. A new functional 5-HT2Areceptor activation assay showed no functional agonistic but some antagonistic effects of 1against the 5-HT-dependent 5-HT2Aactivation and likely antagonistic effects on putative constitutive activity of the 5-HT2Areceptor.