Girolline is a sequence context-selective modulator of eIF5A activity.

Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown.

Potential of Marine Sponge Metabolites against Prions: Bromotyrosine Derivatives, a Family of Interest.

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (), aplysamine-2 (), pseudoceratinine A (), aerophobin-2 (), aplysamine-1 (), and pseudoceratinine B () for the first time from the Wallisian sponge . We then tested compounds - and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of -, , , aplyzanzine C (), purealidin A (), psammaplysenes D () and F (), anomoian F (), and N,N-dimethyldibromotyramine ().

Chemical Investigation of the Calcareous Marine Sponge , Clathridine-A Related Derivatives Isolation, Synthesis and Osteogenic Activity.

As a result of screening a panel of marine organisms to identify lead molecules for the stimulation of endochondral bone formation, the calcareous sponge was identified to exhibit significant activity during endochondral differentiation. On further molecular networking analysis, dereplication and chemical fractionation yielded the known clathridine A-related metabolites and the homodimeric complex (clathridine A) Zn (), together with the new unstable heterodimeric complex (clathridine A-clathridimine)Zn (). With the presence of the zinc complexes annotated through the LC-MS analysis of the crude extract changing due to the instability of some metabolites and complexes constituting the mixture, we combined the isolation of the predicted molecules with their synthesis in order to confirm their structure and to understand their reactivity.

Isolation, Synthesis and Absolute Configuration of the Pericharaxins A and B, Epimeric Hydroxy-Polyene Glycerol Ethers from the Calcarean Sponge .

Naturally occurring epimeric hydroxy-polyene glycerol ether pericharaxins A () and B () were isolated from the calcarean sponge . The structural and stereochemical characterization of both diastereoisomers were established on the basis of spectroscopic data analysis and total synthesis in seven steps. The mixture of pericharaxins A () and B () was proven to be epimeric by chiral-phase HPLC analysis of both synthetic and natural samples.

Bioactive Bromotyrosine Derivatives from the Pacific Marine Sponge (Pulitzer-Finali, 1982).

Chemical investigation of the South-Pacific marine sponge led to the isolation of eight new bromotyrosine metabolites named subereins 1-8 (-) along with twelve known co-isolated congeners. The detailed configuration determination of the first representative major compound of this family 11--fistularin-3 (11,17) () is described. Their chemical characterization was achieved by HRMS and integrated 1D and 2D NMR (nuclear magnetic resonance) spectroscopic studies and extensive comparison with literature data.

Quorum Sensing Inhibitory and Antifouling Activities of New Bromotyrosine Metabolites from the Polynesian Sponge n. sp.

Four new brominated tyrosine metabolites, aplyzanzines C-F (-), were isolated from the French Polynesian sponge n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A () and previously isolated, respectively, from the sponges and Verongula sp.

New Antimalarial and Antimicrobial Tryptamine Derivatives from the Marine Sponge .

Chemical study of the CH₂Cl₂-MeOH (1:1) extract of the sponge collected in Mayotte highlighted three new tryptophan derived alkaloids, 6,6'-bis-(debromo)-gelliusine F (), 6-bromo-8,1'-dihydro-isoplysin A () and 5,6-dibromo-8,1'-dihydro-isoplysin A (), along with the synthetically known 8-oxo-tryptamine () and the three known molecules from the same family, tryptamine (), ()-6-bromo-2'-demethyl-3'--methylaplysinopsin () and ()-6-bromo-2'-demethyl-3'--methylaplysinopsin (). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their antimicrobial and their antiplasmodial activities.

Synergistic AML Cell Death Induction by Marine Cytotoxin (+)-1(), 6(), 1'(), 6'(), 11(), 17()-Fistularin-3 and Bcl-2 Inhibitor Venetoclax.

Treatment of acute myeloid leukemia (AML) patients is still hindered by resistance and relapse, resulting in an overall poor survival rate. Recently, combining specific B-cell lymphoma (Bcl)-2 inhibitors with compounds downregulating myeloid cell leukemia (Mcl)-1 has been proposed as a new effective strategy to eradicate resistant AML cells. We show here that 1(), 6(), 1'(), 6'(), 11(), 17()-fistularin-3, a bromotyrosine compound of the fistularin family, isolated from the marine sponge , synergizes with Bcl-2 inhibitor ABT-199 to efficiently kill Mcl-1/Bcl-2-positive AML cell lines, associated with Mcl-1 downregulation and endoplasmic reticulum stress induction.

Bioactive Bromotyrosine-Derived Alkaloids from the Polynesian Sponge .

Herein, we describe the isolation and spectroscopic identification of eight new tetrabrominated tyrosine alkaloids ⁻ from the Polynesian sponge , along with known major compound psammaplysene D (), ,-dimethyldibromotyramine, 5-hydroxy xanthenuric acid, and xanthenuric acid. Cytotoxicity and acetylcholinesterase inhibition activities were evaluated for some of the isolated metabolites. They exhibited moderate antiproliferative activity against KB cancer cell lines, but psammaplysene D () displayed substantial cytotoxicity as well as acetylcholinesterase inhibition with IC values of 0.

C2'-F Stereoconfiguration As a Puckering Switch for Base Stacking at the Dinucleotide Level.

Fluorine configuration at C2' of the bis(2'-fluorothymidine) dinucleotide is demonstrated to drive intramolecular base stacking. 2'-β F-Configuration drastically reduces stacking compared to the 2'-α series. Hence, base stacking emerges as being tunable by the C2'-F stereoconfiguration through dramatic puckering variations scrutinized by NMR and natural bond orbital analysis.

Unguiculins A-C: cytotoxic bis-guanidine alkaloids from the French Polynesian sponge, Monanchora n. sp.

Two new acyclic bis-guanidine alkaloids, unguiculins B-C (2-3), were isolated from a French Polynesian sponge Monanchora n. sp. together with the known compound unguiculin A (1).

Orbicularisine: A Spiro-Indolothiazine Isolated from Gills of the Tropical Bivalve Codakia orbicularis.

A novel spiro-indolofuranone fused to a thiazine skeleton, orbicularisine (1), was isolated from gills of the mollusk Codakia orbicularis. The isolation and structure elucidation using spectroscopic evidence including mass and NMR spectroscopy are described. The final structure of 1 was supported by key HMBC correlation.

Metabolomics approach to chemical diversity of the Mediterranean marine sponge Agelas oroides.

The Mediterranean marine sponge Agelas oroides is known to contain a large quantity of oroidin, a deterrent, antifouling and antibiofilm pyrrole-2-aminoimidazole. In contrast with other tropical specimens, the chemical composition of Mediterranean Agelas oroides is surprisingly relatively poor in other related metabolites. In the course of finding novel marine natural products, LC-MS based metabolomics study of the Mediterranean Agelas oroides, however, revealed that next to the major compound oroidin, the sponge contains in fact a great diversity of known pyrrole-imidazole alkaloids in minute amounts.

Aedes aegypti Larvicidal Sesquiterpene Alkaloids from Maytenus oblongata.

Four new sesquiterpene alkaloids (1-4) with a β-dihydroagrofuran skeleton and a new triterpenoid (5) were isolated from an ethyl acetate extract of Maytenus oblongata stems. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and ECD experiments. The M.

Cytotoxic Guanidine Alkaloids from a French Polynesian Monanchora n. sp. Sponge.

Four bicyclic and three pentacyclic guanidine alkaloids (1-7) were isolated from a French Polynesian Monanchora n. sp. sponge, along with the known alkaloids monalidine A (8), enantiomers 9-11 of known natural product crambescins, and the known crambescidins 12-15.

Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3',4',5'-Pentamethoxyflavone Isolated from Lantana ukambensis.

Lantana ukambensis (Vatke) Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population.

Netamines O-S, Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei, and Their Antimalarial Activities.

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O - S (1-5, resp.), have been identified together with the known compounds netamine E (6) and mirabilin J (7). The structures of all new netamines were assigned on the basis of spectroscopic analyses.

Quorum sensing inhibitors from Leucetta chagosensis Dendy, 1863.

Unlabelled: Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes.

A minute amount of s-puckered sugars is sufficient for (6-4) photoproduct formation at the dinucleotide level.

The di-2'-α-fluoro analogue of thymidylyl(3',5')thymidine, synthesized to probe the effect of a minimum amount of S conformer on the photoreactivity of dinucleotides, is endowed with only 3% and 8% of S sugar conformation at its 5'- and 3'-end, respectively. This analogue gives rise to the (6-4) photoproduct as efficiently as the dithymine dinucleotide (74% and 66% at the 5'- and 3'-end, respectively) under 254 nm. Our results suggest that the 5'-N, 3'-S conformer gives rise to the (6-4) photoproduct.

Agelastatin E, agelastatin F, and benzosceptrin C from the marine sponge Agelas dendromorpha.

The study of the n-butanol extract of the New Caledonian sponge Agelas dendromorpha led to the isolation and identification of three new pyrrole-2-aminoimidazole (P-2-AI) alkaloids, named agelastatins E (3) and F (4) and benzosceptrin C (5), together with 10 known metabolites, agelastatin A (1), agelastatin D (2), sceptrin (6), manzacidin A, tauroacidin A, taurodispacamide A, nortopsentin D, thymine, longamide, and 4,5-dibromopyrrole-2-carboxamide. Their structures were assigned by spectroscopic data interpretation. All the compounds were tested for cytotoxic activity.

Benzosceptrins A and B with a unique benzocyclobutane skeleton and nagelamide S and T from Pacific sponges.

Four new dimeric pyrrole-2-aminoimidazole alkaloids have been isolated from the Pacific marine sponges Agelas cf. mauritiana and Phakellia sp. They include the unusual C2 symmetrical benzosceptrins A (4) and B (5), which each possess a unique benzocyclobutane skeleton and nagelamides S (6) and T (7).

Axiphenylalaninium and axityrosinium, modified amino acids from the Mediterranean marine sponge Axinella polypoides.

Two new modified amino acids, axiphenylalaninium (1) and axityrosinium (2), along with four known metabolites, C2-alpha-D-mannosylpyranosyl-L-tryptophan (3), N3,5'-cycloxanthosine (4), palythine (5), and taurine, were isolated from the marine sponge Axinella polypoides collected in the Mediterranean Sea. The structures were determined by spectroscopic studies and confirmed by X-ray analysis and chemical modifications.

The sugar conformation governs (6-4) photoproduct formation at the dinucleotide level.

The LNA dinucleotide mimic of TpT whose two-sugar puckers are locked in the C3'-endo conformation selectively produces the corresponding cyclobutane pyrimidine dimer under 254 nm irradiation. In the natural series (TpT) the sugar puckers are in a major C2'-endo sugar conformation and the (6-4) photoproduct is also produced. Consequently, this study demonstrates that the C2'-endo conformation of the sugar pucker is necessary for (6-4) photoproduct formation.

Dinucleotide TpT and its 2'-O-Me analogue possess different backbone conformations and flexibilities but similar stacked geometries.

UV irradiation at 254 nm of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine (1a) and of natural thymidylyl(3'-5')thymidine (1b) generates the same photoproducts (CPD and (6-4)PP; responsible for cell death and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein) to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for 1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowed with different predominant sugar conformations, C3'-endo (1a) and C2'-endo (1b).