000K  utf8
1100  $c2018
1500  eng
2050  urn:nbn:de:gbv:8-mods-2019-00169-2
2051  10.3390/md16080268
3000  Li, Fengjie
3010  Janussen, Dorte
3010  Peifer, Christian
3010  Pérez-Victoria, Ignacio
3010  Tasdemir, Deniz
4000  Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity  [Li, Fengjie]
4209  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.
4950  https://doi.org/10.3390/md16080268$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8-mods-2019-00169-2$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00000147
5051  610
5550  Animals
5550  Antarctica
5550  Antineoplastic Agents
5550  Deep-sea
5550  Doxorubicin
5550  Humans
5550  Keratinocytes
5550  Latrunculia, Molecular Networking
5550  Marine sponge
5550  Molecular docking
5550  Molecular Models
5550  Molecular Structure
5550  Porifera
5550  Protein Conformation
5550  Pyrroles
5550  Quinolines
5550  Tsitsikammamine
5550  Tumor Cell Line
5550  Type I DNA Topoisomerases