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

• Published in: Bioorganic & medicinal chemistry Vol. 30; p. 115950
• Main Authors: Fayez, Shaimaa, Cacciatore, Alessia, Sun, Sijia, Kim, Minjo, Aké Assi, Laurent, Feineis, Doris, Awale, Suresh, Bringmann, Gerhard
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.01.2021
• Subjects: Ancistrobrevidines; Ancistrobreviquinones; Ancistrocladus abbreviatus; Anticancer agents; Naphthylisoquinoline alkaloids; Pancreatic cancer; Ancistrobrevidines; Naphthylisoquinoline alkaloids; Anticancer agents; Ancistrobreviquinones; Ancistrocladus abbreviatus; Pancreatic cancer
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2020.115950

[Display omitted] •Eight new axially chiral alkaloids were isolated from Ancistrocladus abbreviatus.•The series comprises alkaloids of three different subclasses of naphthylisoquinolines.•Two of them are the very first naphthylisoquinolines with a 3,4-naphthoquinone portion.•Ancistrobrevine C eliminates the tolerance of pancreatic cancer cells to nutrition starvation.•Ancistrobrevine C is a potent antiausterity agent with antimetastatic activity. 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-configuration 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 ancistrobrevidines 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 naphthylisoquinolines. In the roots of A. abbreviatus, two further unprecedented 5,1′-coupled alkaloids were discovered, 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.