Promorphinan and bisaporphine alkaloids from Alseodaphne peduncularis

Five previously undescribed benzylisoquinoline alkaloids were isolated from the leaves and stem-bark of Alseodaphne peduncularis. Among these, alseodaphnine (1) was characterized as a tetracyclic rearranged promorphinan alkaloid. Alseodaphnilarines A, B, and C (2–4) were identified as promorphinan-amine conjugates, while alseodaphnidine (5) represents a bisaporphine alkaloid. Additionally, (−)-9,10-dihydrocepharatine A (6) was isolated from a natural source for the first time, although it was previously reported as a byproduct from a total synthesis to cepharatine A. Twelve other known benzylisoquinoline alkaloids (7–18) were also identified. The chemical structures and absolute configurations of compounds 1–5 were elucidated through comprehensive spectroscopic analyses. In vitro cytotoxic assays revealed that alkaloid 14 showed moderate anti-cancer activity against pancreatic and breast cancer cell lines (IC₅₀ 12.6–21.7 μM). Compound 5 demonstrated selective butyrylcholinesterase inhibition (IC₅₀ 21.2 μM), with no activity against acetylcholinesterase. Furthermore, alkaloids 1, 7–9, 14, and 17 significantly extended the lifespan of Caenorhabditis elegans by up to 12 % compared to the control group.