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

Abstract

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.

• Authors: Shaimaa Fayez, Alessia Cacciatore, Sijia Sun, Minjo Kim, Laurent Aké Assi, Doris Feineis, Suresh Awale, Gerhard Bringmann
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 30 Pg. 115950 (01 15 2021) ISSN: 1464-3391 [Electronic] England
• PMID: 33383442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Magnoliopsida (chemistry)
• Molecular Conformation
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Plant Leaves (chemistry)
• Plant Roots (chemistry)
• Structure-Activity Relationship