In a joint effort, researchers from the University of Würzburg, the University of Kinshasa, the Swiss Tropical and Public Health Institute and the University of Basel have isolated and identified three formerly unknown alkaloids.

Alkaloids are, in laymen’s (and laywomen’s) terms, naturally occurring organic compounds of the secondary metabolism, which exhibit a range of pharmacological activities in animals and humans. Even though alkaloids are chemically heterogeneous, they are mostly alkaline, nitrogen-containing compounds.

The newly discovered alkaloids go under the name ealapasamines, derived from their plant of origin, Ancistrocladus ealaensis, and the Lingala word for twins (pasa). Ancistrocladus ealaensis is a tropical plant native to the Northwestern part of the Democratic Republic of Congo whose chemical constituents have so far been studied only scarcely.

Now at once three alkaloids with the molecular formula C48H52N2O8 and differing structure have been isolated from the leaves of this plant.Their most populated conformers were calculated from density functional theory using ORCA.

From a chemical viewpoint, the newly discovered alkaloids are noteworthy because of their structure alone. The ealapasamines are heterodimeric naphthylisoquinoline alkaloids and the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. The newly discovered dimers contain six chiral elements: four stereogenic centers and two outer axes. The stereostructures of the ealapasamines were determined through a combination of spectroscopic methods and chemical and chiroptical investigations. In particular, high resolution electrospray ionisation mass spectroscopy (HRESIMS) in combination with one-dimensional and two-dimensional nuclear magnetic resonance and oxidative degradation as well as electron circular dichroism investigations were carried out.

From a pharmacological (and human) view point, ealapasamines are of interest due to their high antiplasmodial activities. In particular, they exhibit excellent maximum inhibition concentration values in the low nanomolar range. The efficacy of the newly discovered ealapasamines against the pathogens causing malaria tropica, leishmaniasis, Chaga’s disease and African sleeping sickness has been tested. Remarkably high activities were recorded against Plasmodium falcifarum, the deadliest pathogen of malaria tropica.

D. Tshitenge Tshitenge, D. Feineis, V. Mudogo, M. Kaiser, R. Brun, G. Bringmann: “Antiplasmodial Ealapasamines A-C,‘Mixed’ Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis”, Scientific Reports 7, 5767 (2017)