Mbandakamine-Type Naphthylisoquinoline Dimers and Related Alkaloids from the Central African Liana Ancistrocladus ealaensis with Antiparasitic and Antileukemic Activities

  • J Nat Prod. 2018 Apr 27;81(4):918-933. doi: 10.1021/acs.jnatprod.7b01041.
Dieudonné Tshitenge Tshitenge  1  2 ,  Doris Feineis  1 ,  Virima Mudogo  3 ,  Marcel Kaiser  4  5 ,  Reto Brun  4  5 ,  Ean-Jeong Seo  6 ,  Thomas Efferth  6 ,  Gerhard Bringmann  1
Affiliations
  • 1. Institute of Organic Chemistry , University of Würzburg , Am Hubland , D-97074 Würzburg , Germany.
  • 2. Faculty of Pharmaceutical Sciences , University of Kinshasa , B.P. 212 Kinshasa XI, Democratic Republic of the Congo.
  • 3. Faculté des Sciences , Université de Kinshasa , B.P. 202, Kinshasa XI, Democratic Republic of the Congo.
  • 4. Swiss Tropical and Public Health Institute , Socinstrasse 57 , CH-4002 Basel , Switzerland.
  • 5. University of Basel , Petersplatz 1 , CH-4003 Basel , Switzerland.
  • 6. Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology , University of Mainz , Staudinger Weg 5 , D-55128 Mainz , Germany.
PMID: 29560715 DOI: 10.1021/acs.jnatprod.7b01041
Abstract

Four new dimeric naphthylisoquinoline Alkaloids, michellamine A5 (2) and mbandakamines C-E (4-6), were isolated from the Congolese plant Ancistrocladus ealaensis, along with the known dimer mbandakamine A (3). They represent constitutionally unsymmetric dimers, each consisting of two 5,8'-coupled naphthylisoquinoline monomers. While the molecular halves of michellamine A5 (2) are linked via C-6' of both of the naphthalene moieties, i.e., via the least-hindered positions, so that the central biaryl axis is configurationally unstable and not an additional element of chirality, the mbandakamines 3-6 possess three consecutive stereogenic axes. Their monomeric units are linked through an unprecedented 6',1″-coupling in the binaphthalene core, leading to a high steric load, since the central axis is located in one of the peri-positions, neighboring one of the outer axes. In addition, four new 5,8'-coupled monomeric naphthylisoquinolines, viz., ancistroealaines C-F (7-10), were identified, along with four "naphthalene-devoid" tetra- and dihydroisoquinolines, named ealaines A-D (11-14). The new mbandakamines C (4) and D (5) showed pronounced activities against the malaria parasite Plasmodium falciparum, and they were likewise found to display strong cytotoxic activities against human leukemia (CCRF-CEM) and multi-drug-resistant tumor cells (CEM/ADR5000).