Jozilebomines A and B, naphthylisoquinoline dimers from the Congolese liana Ancistrocladus ileboensis, with antiausterity activities against the PANC-1 human pancreatic cancer cell line

Journal article

Two new naphthylisoquinoline dimers, jozilebomines A (1a) and B (1b), were isolated from the roots of the Congolese plant Ancistrocladus ileboensis, along with the known dimer jozimine A2 (2). These compounds are Dioncophyllaceae-type metabolites, i.e., lacking oxygen functions at C-6 and with an R-configuration at C-3 in their tetrahydroisoquinoline moieties. The dimers 1a and 1b consist of two 7,1′-coupled naphthylisoquinoline monomers linked through an unprecedented 3′,6″-coupling in the binaphthalene core and not, as in 2, via the C-3-positions of the two naphthalene units. Thus, different from the C2-symmetric jozimine A2 (2), the new jozilebomines are constitutionally unsymmetric. The central biaryl axis of each of the three dimers is rotationally hindered, so that 1a, 1b, and 2 possess three consecutive chiral axes. The two jozilebomines have identical constitutions and the same absolute configurations at all four stereogenic centers, but differ from each other in their axial chirality. Their structural elucidation was achieved by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and calculated ECD data. They exhibited distinct and specific antiplasmodial activities. All dimers showed potent cytotoxicity against HeLa human cervical cancer cells and preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions. Furthermore, these dimers significantly inhibited the colony formation of PANC-1 cells, even when exposed to noncytotoxic concentration for a short time. Jozilebomines A (1a) and B (1b) and jozimine A2 (2) represent novel potential candidates for future drug development against pancreatic cancer.

Authors: Li, J; Seupel, R; Bruhn, T; Feineis, D; Kaiser, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: Journal of Natural Products
• Volume: 80
• Issue: 10
• Pages: 2807–2817
• Publication date: 2017-10-18
• Acceptance date: 2017-10-18
• DOI: 10.1021/acs.jnatprod.7b00650
• EISSN: 1520-6025
• ISSN: 0163-3864
• Pmid: 29043798
• Language: English
• Keywords: nuclear magnetic resonance, biomolecular; plasmodium falciparum; hela cells; Congo; leishmania donovani; rats; antimalarials; drug screening assays, antitumor; animals; naphthalenes; Magnoliopsida; trypanosoma brucei rhodesiense; antineoplastic agents, phytogenic; molecular structure; pancreatic neoplasms; humans; alkaloids; trypanosoma cruzi; isoquinolines; algorithms; tumor cells, cultured