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.