RRC ID 71774
Author Fayez S, Cacciatore A, Sun S, Kim M, Aké Assi L, Feineis D, Awale S, Bringmann G.
Title Ancistrobrevidines A-C and related naphthylisoquinoline alkaloids with cytotoxic activities against HeLa and pancreatic cancer cells, from the liana Ancistrocladus abbreviatus.
Journal Bioorg Med Chem
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.
Volume 30
Pages 115950
Published 2021-1-15
DOI 10.1016/j.bmc.2020.115950
PII S0968-0896(20)30780-X
PMID 33383442
MeSH Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / isolation & purification Antineoplastic Agents, Phytogenic / 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 Plant Extracts / isolation & purification Plant Extracts / pharmacology* Plant Leaves / chemistry Plant Roots / chemistry Structure-Activity Relationship
IF 3.073
Human and Animal Cells HeLa(RCB0007)