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

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.

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New Discorhabdin Alkaloids from the Antarctic Deep-Sea Sponge Latrunculia biformis

Marine Drugs ◽

10.3390/md17080439 ◽

2019 ◽

Vol 17 (8) ◽

pp. 439 ◽

Cited By ~ 6

Author(s):

Li ◽

Peifer ◽

Janussen ◽

Tasdemir

Keyword(s):

Anticancer Activity ◽

Deep Sea ◽

Topoisomerase I ◽

Active Sites ◽

Binding Potential ◽

Chemical Structures ◽

Ic50 Values ◽

Ft Ir ◽

The Antarctic

The sponge genus Latrunculia is a prolific source of discorhabdin type pyrroloiminoquinone alkaloids. In the continuation of our research interest into this genus, we studied the Antarctic deep-sea sponge Latrunculia biformis that showed potent in vitro anticancer activity. A targeted isolation process guided by bioactivity and molecular networking-based metabolomics yielded three known discorhabdins, (−)-discorhabdin L (1), (+)-discorhabdin A (2), (+)-discorhabdin Q (3), and three new discorhabdin analogs (−)-2-bromo-discorhabdin D (4), (−)-1-acetyl-discorhabdin L (5), and (+)-1-octacosatrienoyl-discorhabdin L (6) from the MeOH-soluble portion of the organic extract. The chemical structures of 1–6 were elucidated by extensive NMR, HR-ESIMS, FT-IR, [α]D, and ECD (Electronic Circular Dichroism) spectroscopy analyses. Compounds 1, 5, and 6 showed promising anticancer activity with IC50 values of 0.94, 2.71, and 34.0 µM, respectively. Compounds 1–6 and the enantiomer of 1 ((+)-discorhabdin L, 1e) were docked to the active sites of two anticancer targets, topoisomerase I-II and indoleamine 2,3-dioxygenase (IDO1), to reveal, for the first time, the binding potential of discorhabdins to these proteins. Compounds 5 and 6 are the first discorhabdin analogs with an ester function at C-1 and 6 is the first discorhabdin bearing a long-chain fatty acid at this position. This study confirms Latrunculia sponges to be excellent sources of chemically diverse discorhabdin alkaloids.

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New Discorhabdin B Dimers with Anticancer Activity from the Antarctic Deep-Sea Sponge Latrunculia biformis

Marine Drugs ◽

10.3390/md18020107 ◽

2020 ◽

Vol 18 (2) ◽

pp. 107 ◽

Cited By ~ 3

Author(s):

Fengjie Li ◽

Dorte Janussen ◽

Deniz Tasdemir

Keyword(s):

Anticancer Activity ◽

Deep Sea ◽

Cancer Cell Line ◽

Human Colon ◽

Colon Cancer Cell Line ◽

Human Colon Cancer ◽

Chemical Structures ◽

Ic50 Values ◽

The Antarctic

Latrunculia sponges represent a rich source of discorhabdin-type pyrroloiminoquinone alkaloids, a few of which comprise a dimeric structure. The anticancer-activity-guided isolation of the n-hexane subextract of the Antarctic deep-sea sponge Latrunculia biformis yielded the known compound (−)-(1R,2R,6R,8S,6’S)-discorhabdin B dimer (1) and two new derivatives, (−)-(1S,2R,6R,8S,6’S)-discorhabdin B dimer (2) and (−)-(1R,2R,6R,8S,6’S)-16’,17’-dehydrodiscorhabdin B dimer (3). The chemical structures of compounds 1–3 were elucidated by means of HR-ESIMS, NMR, [α]D, ECD spectroscopy, and a comparison with the previously reported discorhabdin analogs. Compounds 1 and 2 showed significant in vitro anticancer activity against the human colon cancer cell line (HCT-116), with IC50 values of 0.16 and 2.01 µM, respectively. Compared to monomeric discorhabdins, dimeric discorhabdins are very rare in Nature. This study adds two new discorhabdin dimers (2 and 3) to this small pyrroloiminoquinone subfamily. This is also the first report of compound 1 as a natural product and the first assessment of its in vitro anticancer activity.

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Molecular Networking Reveals Two Distinct Chemotypes in Pyrroloiminoquinone-Producing Tsitsikamma favus Sponges

Marine Drugs ◽

10.3390/md17010060 ◽

2019 ◽

Vol 17 (1) ◽

pp. 60 ◽

Cited By ~ 10

Author(s):

Jarmo-Charles Kalinski ◽

Samantha Waterworth ◽

Xavier Siwe Noundou ◽

Meesbah Jiwaji ◽

Shirley Parker-Nance ◽

...

Keyword(s):

Topoisomerase I ◽

Biosynthetic Pathway ◽

Dna Intercalation ◽

Chemical Characteristics ◽

Taxonomic Identification ◽

Human Cell Lines ◽

Molecular Networking ◽

Drug Leads ◽

Related Compounds ◽

Chromatographic Isolation

The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.

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Isolation of New Glycosides from Anemarrhena Asphodeloides Rhizome and Screening of their Anticancer Activity

Letters in Organic Chemistry ◽

10.2174/1570178615666181102125553 ◽

2019 ◽

Vol 16 (6) ◽

pp. 474-477 ◽

Cited By ~ 1

Author(s):

Pham Van Khang ◽

Nguyen Thi Hien Lan ◽

Le Quang Truong ◽

Mai Thi Minh Chau ◽

Mai Xuan Truong ◽

...

Keyword(s):

Anticancer Activity ◽

Spectral Data ◽

Cell Lines ◽

Cancer Cell ◽

Spectroscopic Analysis ◽

2D Nmr ◽

Ic50 Values ◽

Nmr Techniques ◽

Inhibitory Activities ◽

Anemarrhena Asphodeloides

In this report, two new steroidal glycosides were isolated and determined from n-butanol fraction of A.asphodeloides. The structures were confirmed in comparison with the spectral data of known compounds by using different spectroscopic analysis approaches including 1D & 2D-NMR techniques and HRMS. The anti-proliferation screening against cancer cell lines A549 and HeLa indicated that compound 1 exhibited good inhibitory activities with IC50 values of 0.79 and 0.55 µg/mL, respectively.

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Phenylhydrazone and Quinazoline Derivatives from the Cold-Seep-Derived Fungus Penicillium oxalicum

Marine Drugs ◽

10.3390/md19010009 ◽

2020 ◽

Vol 19 (1) ◽

pp. 9

Author(s):

Ya-Ping Liu ◽

Sheng-Tao Fang ◽

Zhen-Zhen Shi ◽

Bin-Gui Wang ◽

Xiao-Nian Li ◽

...

Keyword(s):

Deep Sea ◽

Spectroscopic Data ◽

2D Nmr ◽

Penicillium Oxalicum ◽

Marine Phytoplankton ◽

Cold Seep ◽

Phytoplankton Species ◽

X Ray ◽

X Ray Crystallography ◽

Quinazoline Derivatives

Three new phenylhydrazones, penoxahydrazones A–C (compounds 1–3), and two new quinazolines, penoxazolones A (compound 4) and B (compound 5), with unique linkages were isolated from the fungus Penicillium oxalicum obtained from the deep sea cold seep. Their structures and relative configurations were assigned by analysis of 1D/2D NMR and mass spectroscopic data, and the absolute configurations of 1, 4, and 5 were established on the basis of X-ray crystallography or ECD calculations. Compound 1 represents the first natural phenylhydrazone-bearing steroid, while compounds 2 and 3 are rarely occurring phenylhydrazone tautomers. Compounds 4 and 5 are enantiomers that feature quinazoline and cinnamic acid units. Some isolates exhibited inhibition of several marine phytoplankton species and marine-derived bacteria.

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An Antarctic shelf population of the deep-sea, Pacific brachiopod Neorhynchia strebeli

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315400071757 ◽

1997 ◽

Vol 77 (2) ◽

pp. 399-407 ◽

Cited By ~ 7

Author(s):

David K.A. Barnes ◽

Lloyd S. Peck

Keyword(s):

Deep Sea ◽

Growth Function ◽

Weddell Sea ◽

Von Bertalanffy ◽

Growth Rings ◽

Von Bertalanffy Growth Function ◽

Annual Periodicity ◽

A Site ◽

The Antarctic ◽

Order Rhynchonellida

Thirty-five specimens of the articulate brachiopod Neorhynchia strebeli were collected from a site at 814 m in the Weddell Sea. This was only the second species of the order Rhynchonellida to be found in Antarctica. Formerly N. strebeli was known solely from abyssal Pacific Ocean localities. A circumantarctic distribution is suggested in addition to the known deep-sea Pacific range. The specimens of this collection showed considerable commissure variation, suggesting that the previously proposed erection of two subspecies on the basis of this character is erroneous, and emphasises the phenotypic plasticity of some articulate brachiopods. The valve lengths and the number of alpha growth rings in the sample showed a normal distribution and a von Bertalanffy growth function was fitted to the data: Lt = 23 (1-exp[-0·228t]). If the alpha growth rings were of annual periodicity, the ages attained by the Antarctic N. strebeli of 11 y would be substantially lower than those reported for other Weddell Sea brachiopods. The epibiotic communities occurring on the valves of N. strebeli were impoverished, which is characteristic of deep water Antarctic brachiopods. The few specimens collected with their substratum were attached to small pebbles, but the typical attachment substrata may be different.

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