Ancistrobrevidines A-C and related naphthylisoquinoline alkaloids with cytotoxic activities against HeLa and pancreatic cancer cells, from the liana Ancistrocladus abbreviatus

Authors: Fayez S, Cacciatore A, Bringmann G.

Bioorganic & Medicinal Chemistry Volume 30, 2021


From the leaves of Ancistrocladus abbreviatus (Ancistrocladaceae), six 5,1′-coupled naphthyldihydroisoquinoline alkaloids were isolated, ancistrobrevidines A-C (5–7), 5-epi-dioncophyllidine C2 (10), 6-O-methylhamatinine (8), and 6-O-methylancistectorine A3 (9); the two latter compounds were already known from related plants. Most strikingly, this series comprises alkaloids belonging to three different subclasses of naphthylisoquinolines. Ancistrobrevidine C (7) and the alkaloids 8 and 9, displaying the S-configuration at C-3 and an oxygen function at C-6, are three further representatives of the large subgroup of 5,1′-coupled Ancistrocladaceae-type compounds found in nature. 5-epi-Dioncophyllidine C2 (10), lacking an oxygen function at C-6 and having the R-configu-ration at C-3, is only the third representative of a 5,1′-linked Dioncophyllaceae-type naphthylisoquinoline. Likewise rare are 5,1′-coupled hybrid-type alkaloids, which are 6-oxygenated and 3R-configured. The ancis-trobrevidines A (5) and B (6) are the only second and third examples of such 5,1′-linked naphthylisoquinolines in Ancistrocladus species showing the landmarks of both, Ancistrocladaceae- and Dioncophyllaceae-type naph-thylisoquinolines. In the roots of A. abbreviatus, two further unprecedented 5,1′-coupled alkaloids were discov-ered, ancistrobreviquinones A (11) and B (12), consisting of a 3,4-naphthoquinone portion coupled to a tetrahydroisoquinoline subunit. They are the very first quinoid naphthylisoquinolines possessing an ortho- diketone entity. Ancistrobrevidine C (7) exerted pronounced antiproliferative activities against HeLa cervical cancer cells and preferential cytotoxicity towards PANC-1 human pancreatic cancer cells under nutrient-deprived conditions following the antiausterity approach. Moreover, 7 suppressed the migration of PANC-1 cells and significantly inhibited colony formation under nutrient-rich conditions in a concentration-dependent manner, and induced dramatic alteration in cell morphology, leading to cell death.