title: Dioncophyllines C2, D2, and F and Related Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ileboensis with Potent Activities against Plasmodium falciparum 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 C2(2) and D2(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 D2(3) occur as pairs of configurationally semistable and, thus, slowly interconverting atropo-diastereomers, whereas dioncophylline C2(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.
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.|State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , Urumqi, 830011, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Raina
authors.initials: R
authors.lastname: Seupel
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Feineis
authors.affiliation: Faculté des Sciences, Université de Kinshasa , B.P. 202, Kinshasa XI, Democratic Republic of the Congo.
authors.forename: Virima
authors.initials: V
authors.lastname: Mudogo
authors.affiliation: Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4002 Basel, Switzerland.|University of Basel , Petersplatz 1, CH-4003 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4002 Basel, Switzerland.|University of Basel , Petersplatz 1, CH-4003 Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Daniela
authors.initials: D
authors.lastname: Brünnert
authors.forename: Manik
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, University of Mainz , Staudinger Weg 5, D-55128 Mainz, Germany.
authors.forename: Ean-Jeong
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, University of Mainz , Staudinger Weg 5, D-55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Gerhard
authors.identifier: 0000-0002-3583-5935
authors.initials: G
authors.lastname: Bringmann
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D000970:Antineoplastic Agents; D007546:Isoquinolines; C000621077:dioncophylline C2; C000621078:dioncophylline D2; C000621079:dioncophylline F; C104320:dioncophylline A