2. Academic Validation
  3. A Near-Complete Series of Four Atropisomeric Jozimine A2-Type Naphthylisoquinoline Dimers with Antiplasmodial and Cytotoxic Activities and Related Alkaloids from Ancistrocladus abbreviatus

A Near-Complete Series of Four Atropisomeric Jozimine A2-Type Naphthylisoquinoline Dimers with Antiplasmodial and Cytotoxic Activities and Related Alkaloids from Ancistrocladus abbreviatus

  • J Nat Prod. 2019 Nov 22;82(11):3033-3046. doi: 10.1021/acs.jnatprod.9b00589.
Shaimaa Fayez 1 2,  Jun Li 1 3,  Doris Feineis 1,  Laurent Aké Assi 4,  Marcel Kaiser 5 6,  Reto Brun 5 6,  Mohamed A Anany 7 8,  Harald Wajant 7,  Gerhard Bringmann 1
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry , University of Würzburg , Am Hubland , D-97074 Würzburg , Germany.
  • 2 Department of Pharmacognosy, Faculty of Pharmacy , Ain-Shams University , Organization of African Unity Street 1 , 11566 Cairo , Egypt.
  • 3 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.
  • 4 Centre National de Floristique, Conservatoire et Jardin Botaniques , Université d' Abidjan , Abidjan 08, Ivory Coast.
  • 5 Swiss Tropical and Public Health Institute , Socinstrasse 57 , CH-4002 Basel , Switzerland.
  • 6 University of Basel , Petersplatz 1 , CH-4003 Basel , Switzerland.
  • 7 Division of Molecular Internal Medicine, Department of Internal Medicine II , University Hospital Würzburg , Grombühlstraße 12 , D-97080 Würzburg , Germany.
  • 8 Division of Genetic Engineering and Biotechnology, Department of Microbial Biotechnology , National Research Centre , El Buhouth Street, Dokki , 12622 Giza , Egypt.
PMID: 31642313 DOI: 10.1021/acs.jnatprod.9b00589
Abstract

Three new naphthylisoquinoline dimers, jozibrevines A-C (1a-c), were isolated from the West African shrub Ancistrocladus abbreviatus, along with the known dimer jozimine A2 (1d). The two molecular moieties of 1a-d are coupled via the sterically constrained 3',3″-positions of their two naphthalene units, so that the central biaryl linkage is rotationally hindered. With the two outer axes also being chiral, 1a-d possess three consecutive stereogenic axes. The four isolated dimers all have the same constitutions and identical absolute configurations at the four stereogenic centers, but differ by their axial chirality. They belong to the extremely small class of Dioncophyllaceae-type naphthylisoquinoline dimers, i.e., being devoid of oxygen functions at C-6 and bearing the R-configuration at C-3 in their isoquinoline portions. Besides these dimers, the plant produces predominantly typical Ancistrocladaceae-type monomeric compounds, i.e., with the S-configuration at C-3 and an oxygen function at C-6, such as the new ancistrobrevines K (5) and L (6). Furthermore, a new hybrid-type (i.e., mixed Ancistrocladaceae/Dioncophyllaceae-type) alkaloid was identified, named ancistrobrevine M (7), which is 3R-configured and 6-oxygenated. Remarkable was the discovery of its "inverse hybrid-type" counterpart, dioncoline A (8). It is the as yet only known 3S-configured naphthylisoquinoline lacking an O-functionality at C-6. The new jozibrevines A-C (1a-c) exhibited pronounced antiplasmodial activities in the submicromolar range, with 1a being the most potent compound (IC50, 0.012 μM). Furthermore, jozimine A2 (1d) showed cytotoxicity against human colon carcinoma (HT-29), fibrosarcoma (HT1080), and multiple myeloma (MM.1S) Cancer cells, displaying IC50 values of 12.0, 9.0, and 5.0 μM, respectively, whereas jozibrevines A (1a) and B (1b) were nontoxic in this concentration range.

Figures