Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity.

Li, Fengjie, Janussen, Dorte, Peifer, Christian, Pérez-Victoria, Ignacio and Tasdemir, Deniz (2018) Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity. Open Access Marine Drugs, 16 (8). p. 268. DOI 10.3390/md16080268.

[img]
Preview
Text
marinedrugs-16-00268-v2.pdf - Published Version
Available under License Creative Commons: Attribution 4.0.

Download (3365Kb) | Preview
[img]
Preview
Text
marinedrugs-16-00268-s001.pdf - Supplemental Material
Available under License Creative Commons: Attribution 4.0.

Download (1281Kb) | Preview

Supplementary data:

Abstract

The Antarctic deep-sea sponge Latrunculia (Latrunculia) biformis Kirkpatrick, 1908 (Class Demospongiae Sollas, Order Poecilosclerida Topsent, Latrunculiidae Topsent) was selected for chemical analyses due to its potent anticancer activity. Metabolomic analysis of its crude extract by HRMS/MS-based molecular networking showed the presence of several clusters of pyrroloiminoquinone alkaloids, i.e., discorhabdin and epinardin-type brominated pyridopyrroloquinolines and tsitsikammamines, the non-brominated bis-pyrroloiminoquinones. Molecular networking approach combined with a bioactivity-guided isolation led to the targeted isolation of the known pyrroloiminoquinone tsitsikammamine A (1) and its new analog 16,17-dehydrotsitsikammamine A (2). The chemical structures of the compounds 1 and 2 were elucidated by spectroscopic analysis (one-dimensional (1D) and two-dimensional (2D) NMR, HR-ESIMS). Due to minute amounts, molecular modeling and docking was used to assess potential affinities to potential targets of the isolated compounds, including DNA intercalation, topoisomerase I-II, and indoleamine 2,3-dioxygenase enzymes. Tsitsikammamines represent a small class of pyrroloiminoquinone alkaloids that have only previously been reported from the South African sponge genus Tsitsikamma Samaai & Kelly and an Australian species of the sponge genus Zyzzya de Laubenfels. This is the first report of tsitsikammamines from the genus Latrunculia du Bocage and the successful application of molecular networking in the identification of comprehensive chemical inventory of L.biformis followed by targeted isolation of new molecules. This study highlights the high productivity of secondary metabolites of Latrunculia sponges and may shed new light on their biosynthetic origin and chemotaxonomy

Document Type: Article
Keywords: Antarctica; Latrunculia, molecular networking; deep-sea; marine sponge; molecular docking; tsitsikammamine
Research affiliation: OceanRep > GEOMAR > FB3 Marine Ecology > FB3-MN Marine natural products chemistry
Refereed: Yes
Open Access Journal?: Yes
DOI etc.: 10.3390/md16080268
ISSN: 1660-3397
Expeditions/Models/Experiments:
Date Deposited: 11 Dec 2018 11:20
Last Modified: 24 May 2019 12:38
URI: http://oceanrep.geomar.de/id/eprint/44930

Actions (login required)

View Item View Item

Document Downloads

More statistics for this item...