Michellamines A and A, and further mono- and dimeric naphthylisoquinoline alkaloids from a Congolese liana and their antiausterity activities against pancreatic cancer cells.

Michellamines A (1) and A (2) are the first dimers of 5,8'-coupled naphthylisoquinoline alkaloids with -configured stereocenters in both tetrahydroisoquinoline subunits. They were isolated from the leaves of a recently discovered, yet unidentified Congolese liana that shares some morphological characteristics with . Two further new dimeric analogs, michellamines B (3) and B (4), were obtained, along with two previously likewise unknown monomers, ancistrobonsolines A (5) and A (6), which, besides one single known other example, are the only naphthyldihydroisoquinolines with an -configured biaryl axis and -configuration at C-3. Moreover, five compounds earlier reported from other species were identified, ancistroealaine C (7), korupensamines A (8a) and B (8b), and michellamines A (9) and E (10). Their complete structural elucidation succeeded due to the fruitful interplay of spectroscopic, chemical, and chiroptical methods. Chemotaxonomically, the stereostructures of the metabolites clearly delineate this Congolese liana from all known related species, showing that it might be a new taxon. Ancistrobonsolines A (5) and A (6) exhibited strong preferential cytotoxicities against human PANC-1 pancreatic cancer cells under nutrient-deprived conditions, without displaying toxicity in normal, nutrient-rich medium. Against cervical HeLa cancer cells, the dimeric alkaloids michellamines A (1) and E (10) displayed the highest cytotoxic activities, comparable to that of the standard agent, 5-fluorouracil. Furthermore, ancistrobonsolines A (5) and A (6) showed weak-to-moderate antiprotozoal activities.