Pegaharolines A − I, structurally novel indole alkaloids with anti-HSV-2 virus activities from Peganum harmala L. seeds

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A − I (1–9), and 11 known ones (10−20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5–6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1–6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC₅₀ = 0.90 ± 0.10 μM) was much better than that of the positive control (acyclovir, IC₅₀ = 1.12 ± 0.15 μM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products.