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

• Published in: Journal of natural products (Washington, D.C.) Vol. 81; no. 4; pp. 918 - 933
• Main Authors: Tshitenge, Dieudonné Tshitenge, Feineis, Doris, Mudogo, Virima, Kaiser, Marcel, Brun, Reto, Seo, Ean-Jeong, Efferth, Thomas, Bringmann, Gerhard
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 27.04.2018; Amer Chemical Soc
• Subjects: Africa, Central; Alkaloids - pharmacology; Antimalarials - pharmacology; Antineoplastic Agents, Phytogenic; Antiparasitic Agents - pharmacology; Caryophyllales - chemistry; Cell Line, Tumor; Chemistry, Medicinal; Humans; Isoquinolines - pharmacology; Life Sciences & Biomedicine; Naphthalenes - pharmacology; Pharmacology & Pharmacy; Plant Sciences; Plasmodium falciparum - drug effects; Quinolines - pharmacology; Science & Technology; Africa, Central; MICHELLAMINES; ACETOGENIC ISOQUINOLINE ALKALOIDS; GENTRYMINE-B; BIOSYNTHESIS; CHIRAL NATURAL-PRODUCTS; TRIPHYOPHYLLUM-PELTATUM; A-D; DRUG-RESISTANCE; MULTIDRUG-RESISTANCE; ANTIPROTOZOAL
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.7b01041

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).