Michellamines A₆ and A₇, and further mono- and dimeric naphthylisoquinoline alkaloids from a Congolese <i>Ancistrocladus</i> liana and their antiausterity activities against pancreatic cancer cells

Abstract

Michellamines A₆ (1) and A₇ (2) are the first dimers of 5,8'-coupled naphthylisoquinoline alkaloids with <i>cis</i>-configured stereocenters in both tetrahydroisoquinoline subunits. They were isolated from the leaves of a recently discovered, yet unidentified Congolese <i>Ancistrocladus</i> liana that shares some morphological characteristics with <i>Ancistrocladus likoko</i>. Two further new dimeric analogs, michellamines B₄ (3) and B₅ (4), were obtained, along with two previously likewise unknown monomers, ancistrobonsolines A₁ (5) and A₂ (6), which, besides one single known other example, are the only naphthyldihydroisoquinolines with an <i>M</i>-configured biaryl axis and <i>R</i>-configuration at C-3. Moreover, five compounds earlier reported from other <i>Ancistrocladus</i> species were identified, ancistroealaine C (7), korupensamines A (8a) and B (8b), and michellamines A₂ (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 <i>Ancistrocladus</i> liana from all known related species, showing that it might be a new taxon. Ancistrobonsolines A₁ (5) and A₂ (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 A₆ (1) and E (10) displayed the highest cytotoxic activities, comparable to that of the standard agent, 5-fluorouracil. Furthermore, ancistrobonsolines A₁ (5) and A₂ (6) showed weak-to-moderate antiprotozoal activities.