Dioncophyllines C₂, D₂, and F and Related Naphthylisoquinoline Alkaloids from the Congolese Liana <i>Ancistrocladus ileboensis</i> with Potent Activities against <i>Plasmodium falciparum</i> and against Multiple Myeloma and Leukemia Cell Lines

Abstract

Dioncophylline F ( 1 ), the first 5,8′-coupled dioncophyllaceous alkaloid (i.e., lacking an oxygen function at C-6 and possessing an R -configuration at C-3), was isolated from the recently described Congolese liana Ancistrocladus ileboensis . Two further, likewise Dioncophyllaceae-type, alkaloids, the dioncophyllines C 2 ( 2 ) and D 2 ( 3 ), were identified, along with the Ancistrocladaceae-type compound ancistrocladisine B ( 4 ), which is oxygenated at C-6 and S -configured at C-3. The structures of the new compounds were determined by spectroscopic, chemical, and chiroptical methods. The stereostructure of 1 was further confirmed by total synthesis. As a consequence of the lack of a methyl group ortho to their biaryl axes, both dioncophylline F ( 1 ) and the 7,8′-coupled dioncophylline D 2 ( 3 ) occur as pairs of configurationally semistable and, thus, slowly interconverting atropo-diastereomers, whereas dioncophylline C 2 ( 2 ), with its 5,1′-linkage, is configurationally stable at the axis. Eight further known naphthylisoquinolines were isolated from A. ileboensis, among them dioncophylline A ( P -10 ), its 4′- O -demethyl analogue P - 11, and 5′- O -methyldioncophylline D ( 7 ), which were found to display strong cytotoxic activities against multiple myeloma INA-6 cells ( P -10 even stronger than the standard drug melphalan) and against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Moreover, the dioncophyllines 1, 3, and 7 showed high—and specific—activities against the malaria parasite Plasmodium falciparum .