Ancistroyafungines A-D, 5,8′- and 5,1′-coupled naphthylisoquinoline alkaloids from a Congolese Ancistrocladus species, with antiausterity activities against human PANC-1 pancreatic cancer cells

Abstract

Four new naphthylisoquinoline alkaloids, the 5,8′-coupled ancistroyafungines A-C (1-3) and the 5,1′-linked ancistroyafungine D (4), have been isolated from the stem bark of an as yet unidentified Ancistrocladus (Ancistrocladaceae) liana recently discovered near the village Yafunga, in the North-Central region of the Democratic Republic of the Congo. Likewise obtained were eleven analogs previously identified in related African and Asian Ancistrocladus species, exhibiting five different coupling types, viz., 5,8′, 5,1′, 7,1′, N,6′, and N,8′. All of the alkaloids are S-configured at C-3 and possess an oxygen function at C-6 in the isoquinoline portion, and, thus, belong to the subclass of “Ancistrocladaceae-type” alkaloids. This finding is geo- and chemotaxonomically remarkable, since – apart from one other Ancistrocladus species from the Central Congo Basin – only Southeast Asian and East African Ancistrocladaceae are known to exclusively produce naphthylisoquinolines with these structural features. Moreover, the alkaloid pattern of this Congolese liana clearly demarcates this plant from all other Ancistrocladus taxa that have so far been botanically described, which suggests that it might represent a new species or subspecies. The new ancistroyafungines display strong preferential cytotoxic activities towards human PANC-1 pancreatic cancer cells in nutrient-deprived medium, without showing toxicity in normal, nutrient-rich conditions.