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