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

Li, Fengjie; Janussen, Dorte; Taşdemir, Deniz

doi:10.3390/md18020107

Cited by 17 publications

(21 citation statements)

References 21 publications

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“…Additionally, also of note were the sub-micromolar activities of 8 , 13 and 17 towards Trypanosoma brucei rhodesiense . In the case of discorhabdin B dimer 17 , it is interesting to contrast the low cytotoxicity towards the non-malignant rat skeletal myoblast cell line L6 (IC 50 41 μM) ( Table 6 ), compared to the recently reported strong cytotoxicity observed for the same compound towards a human colon tumour cell line HCT-116 (IC 50 0.16 μM) and a non-malignant human keratinocyte cell line (IC 50 0.56 μM) [ 5 ].…”

Section: Resultsmentioning

confidence: 96%

“…Together these results prompted us to evaluate the antiparasitic activities of a series of discorhabdin natural products and semi-synthetic analogues that we have previously shown to exhibit modest or minimal tumour cell line cytotoxicity. Included in this study were (+)-discorhabdin B 1 , discorhabdin C 2 , 6 – 8 , 3-dihydrodiscorhabdin C 9 [ 15 ], (+)-discorhabdin D 10 , (-)-discorhabdin H 11 , (+)-discorhabdin H 2 12 [ 19 ] (-)-discorhabdin L 13 , discorhabdin Q 14 , discorhabdin U 15 , semi-synthetic dienone-phenol 16 [ 23 ] and discorhabdin B dimer 17 [ 5 , 16 ] ( Figure 8 ).…”

Section: Resultsmentioning

confidence: 99%

“…Usually derived from extracts of marine sponges of the genus Latrunculia , these alkaloids have attracted much attention from both chemists and biologists due to their complex structures and associated biological activities [ 1 , 2 ]. While some of the first examples of the discorhabdins e.g., discorhabdin B ( 1 ) and C ( 2 ) ( Figure 1 ) were structurally relatively simple [ 3 , 4 ], recent studies have unveiled unusual dimers [ 5 ], oligomers [ 6 ] and more complex polycyclic variants [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Exploration of the Electrophilic Reactivity of the Cytotoxic Marine Alkaloid Discorhabdin C and Subsequent Discovery of a New Dimeric C-1/N-13-Linked Discorhabdin Natural Product

2020

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The cytotoxic marine natural product discorhabdin C contains a 2,6-dibromo-cyclohexa-2,5-diene moiety, previously proposed to be a critical feature required for biological activity. We have determined that the dienone-ring of discorhabdin C is indeed electrophilic, reacting with thiol and amine nucleophiles, affording debrominated adducts. In the case of reaction with 1-aminopentane the product contains an unusual C-2/N-18 ring closed, double-hydrate moiety. This electrophilic reactivity also extends to proteins, with lysozyme-discorhabdin C adducts being detected by ESI mass spectrometry. These results prompted further examination of an extract of discorhabdin C-producing sponge, Latrunculia (Latrunculia) trivetricillata, leading to the isolation and characterisation of a new example of a C-1/N-13 linked discorhabdin dimer that shared structural similarities with the 1-aminopentane-discorhabdin C adduct. To definitively assess the influence of the dienone moiety of discorhabdin C on cytotoxicity, a semi-synthetic hydrogenation derivative was prepared, affording a didebrominated ring-closed carbinolamine that was essentially devoid of tumour cell line cytotoxicity. Antiparasitic activity was assessed for a set of 14 discorhabdin alkaloids composed of natural products and semi-synthetic derivatives. Three compounds, (-)-discorhabdin L, a dimer of discorhabdin B and the discorhabdin C hydrogenation carbinolamine, exhibited pronounced activity towards Plasmodium falciparum K1 (IC50 30–90 nM) with acceptable to excellent selectivity (selectivity index 19–510) versus a non-malignant cell line.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exploration of the Electrophilic Reactivity of the Cytotoxic Marine Alkaloid Discorhabdin C and Subsequent Discovery of a New Dimeric C-1/N-13-Linked Discorhabdin Natural Product

2020

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“…More importantly, MN is able to map out the chemical space of a biological sample by grouping similar metabolites that produce similar MS/MS fragmentation in one cluster [ 15 ]. Our research group has been using MN successfully to uncover the detailed chemical machinery of various marine macro- and micro-organisms followed by targeted isolation of new and bioactive marine natural products [ 14 , 30 , 31 ]. However, in the current study, MN provided limited information on the chemical composition of A. sinoxea and only two natural product families, i.e., phospholipids and steroids, which are the major components of sponge cell walls [ 32 ], have been annotated.…”

Section: Discussionmentioning

confidence: 99%

Integrating Molecular Networking and 1H NMR Spectroscopy for Isolation of Bioactive Metabolites from the Persian Gulf Sponge Axinella sinoxea

Kouchaksaraee

Farimani

et al. 2020

Marine Drugs

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The geographic position, highly fluctuating sea temperatures and hypersalinity make Persian Gulf an extreme environment. Although this unique environment has high biodiversity dominated by invertebrates, its potential in marine biodiscovery has largely remained untapped. Herein, we aimed at a detailed analysis of the metabolome and bioactivity profiles of the marine sponge Axinella sinoxea collected from the northeast coast of the Persian Gulf in Iran. The crude extract and its Kupchan subextracts were tested in multiple in-house bioassays, and the crude extract and its CHCl3-soluble portion showed in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium (Efm). A molecular networking (MN)-based dereplication strategy by UPLC-MS/MS revealed the presence of phospholipids and steroids, while 1H NMR spectroscopy indicated the presence of additional metabolites, such as diketopiperazines (DKPs). Integrated MN and 1H NMR analyses on both the crude and CHCl3 extracts combined with an antibacterial activity-guided isolation approach afforded eight metabolites: a new diketopiperazine, (-)-cyclo(L-trans-Hyp-L-Ile) (8); a known diketopiperazine, cyclo(L-trans-Hyp-L-Phe) (7); two known phospholipids, 1-O-hexadecyl-sn-glycero-3-phosphocholine (1) and 1-O-octadecanoyl-sn-glycero-3-phosphocholine (2); two known steroids, 3β-hydroxycholest-5-ene-7,24-dione (3) and (22E)-3β-hydroxycholesta-5,22-diene-7,24-dione (4); two known monoterpenes, loliolide (5) and 5-epi-loliolide (6). The chemical structures of the isolates were elucidated by a combination of NMR spectroscopy, HRMS and [α]D analyses. All compounds were tested against MRSA and Efm, and compound 3 showed moderate antibacterial activity against MRSA (IC50 value 70 μg/mL). This is the first study that has dealt with chemical and bioactivity profiling of A. sinoxea leading to isolation and characterization of pure sponge metabolites.

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“…Molecular networking-based metabolomics strategy revealed the presence of several putatively new dimeric and trimeric discorhabdins in the n -hexane subextract of the Antarctic deep-sea sponge L. ( L. ) biformis Kirkpatrick, 1908 [ 79 , 98 ]. Targeted isolation efforts yielded three new dimeric discorhabdins, namely, (−)-1- epi -discorhabdin B dimer ( 42 ), (−)-16′,17′-dehydrodiscorhabdin B dimer ( 43 ), and didiscorhabdin ( 44 ), the known (−)-discorhabdin B dimer ( 41 ) and a trimeric molecule tridiscorhabdin ( 45 ) ( Figure 4 ) [ 79 , 98 ]. Their absolute configurations were assigned by comparison of the experimental and the DFT-calculated ECD spectra.…”

Section: Chemical Investigations Of Marine Sponges From Family Latmentioning

confidence: 99%

Chemistry, Chemotaxonomy and Biological Activity of the Latrunculid Sponges (Order Poecilosclerida, Family Latrunculiidae)

Kelly

Taşdemir

2021

Marine Drugs

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Marine sponges are exceptionally prolific sources of natural products for the discovery and development of new drugs. Until now, sponges have contributed around 30% of all natural metabolites isolated from the marine environment. Family Latrunculiidae Topsent, 1922 (class Demospongiae Sollas, 1885, order Poecilosclerida Topsent, 1928) is a small sponge family comprising seven genera. Latrunculid sponges are recognized as the major reservoirs of diverse types of pyrroloiminoquinone-type alkaloids, with a myriad of biological activities, in particular, cytotoxicity, fuelling their exploration for anticancer drug discovery. Almost 100 pyrroloiminoquinone alkaloids and their structurally related compounds have been reported from the family Latrunculiidae. The systematics of latrunculid sponges has had a complex history, however it is now well understood. The pyrroloiminoquinone alkaloids have provided important chemotaxonomic characters for this sponge family. Latrunculid sponges have been reported to contain other types of metabolites, such as peptides (callipeltins), norditerpenes and norsesterpenes (trunculins) and macrolides (latrunculins), however, the sponges containing latrunculins and trunculins have been transferred to other sponge families. This review highlights a comprehensive literature survey spanning from the first chemical investigation of a New Zealand Latrunculia sp. in 1986 until August 2020, focusing on the chemical diversity and biological activities of secondary metabolites reported from the family Latrunculiidae. The biosynthetic (microbial) origin and the taxonomic significance of pyrroloiminoquinone related alkaloids are also discussed.

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

Abstract: Latrunculia sponges represent a rich source of discorhabdin-type pyrroloiminoquinone alkaloids, a few of which comprise a dimeric structure. The anticancer-activity-

Cited by 17 publications

References 21 publications

Exploration of the Electrophilic Reactivity of the Cytotoxic Marine Alkaloid Discorhabdin C and Subsequent Discovery of a New Dimeric C-1/N-13-Linked Discorhabdin Natural Product

Exploration of the Electrophilic Reactivity of the Cytotoxic Marine Alkaloid Discorhabdin C and Subsequent Discovery of a New Dimeric C-1/N-13-Linked Discorhabdin Natural Product

Integrating Molecular Networking and 1H NMR Spectroscopy for Isolation of Bioactive Metabolites from the Persian Gulf Sponge Axinella sinoxea

Chemistry, Chemotaxonomy and Biological Activity of the Latrunculid Sponges (Order Poecilosclerida, Family Latrunculiidae)

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