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.

Organic Matrix and Secondary Metabolites in Nacre.

Nacre, also called mother-of-pearl, is a naturally occurring biomineral, largely studied by chemists, structural biologists, and physicists to understand its outstanding and diverse properties. Nacre is constituted of aragonite nanograins surrounded by organic matrix, and it has been established that the organic matrix is responsible for initiating and guiding the biomineralization process. The first challenge to study the organic matrix of nacre lays in its separation from the biomineral.

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.

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase.

Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analogue EL-228 (), whose structure could be optimized into the potent CJ2-150 (). Here we present the synthesis of new inhibitors of Aurora B kinase, which is an important target for cancer therapy through mitosis regulation.

Discovery of simplified benzazole fragments derived from the marine benzosceptrin B as necroptosis inhibitors involving the receptor interacting protein Kinase-1.

With the aim to develop new chemical tools based on simplified natural metabolites to help deciphering the molecular mechanism of necroptosis, simplified benzazole fragments including 2-aminobenzimidazole and the 2-aminobenzothiazole analogs were prepared during the synthesis of the marine benzosceptrin B. Conpounds inhibiting the RIPK1 protein kinase were discovered. A library of 54 synthetic analogs were prepared and evaluated through a phenotypic screen using the inhibition of the necrotic cell death induced by TNF-α in human Jurkat T cells deficient for the FADD protein.

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.

Chemical Diversity and Biological Activities of Marine Sponges of the Genus : A Systematic Review.

Marine natural products (MNPs) continue to be in the spotlight in the global drug discovery endeavor. Currently, more than 30,000 structurally diverse secondary metabolites from marine sources have been isolated, making MNPs a profound, renewable source to investigate novel drug compounds. Marine sponges of the genus (family: Aplysinellidae) are recognized as producers of bromotyrosine derivatives, which are considered distinct chemotaxonomic markers for the marine sponges belonging to the order Verongida.

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.

Chemistry and Biological Activities of the Marine Sponges of the Genera (), and .

Over the past seven decades, particularly since the discovery of the first marine-derived nucleosides, spongothymidine and spongouridine, from the Caribbean sponge in the early 1950s, marine natural products have emerged as unique, renewable and yet under-investigated pools for discovery of new drug leads with distinct structural features, and myriad interesting biological activities. Marine sponges are the most primitive and simplest multicellular animals, with approximately 8900 known described species, although more than 15,000 species are thought to exist worldwide today. These marine organisms potentially represent the richest pipeline for novel drug leads.

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.

Batzella, Crambe and Monanchora: Highly Prolific Marine Sponge Genera Yielding Compounds with Potential Applications for Cancer and Other Therapeutic Areas.

Pyrroloquinoline and guanidine-derived alkaloids present distinct groups of marine secondary metabolites with structural diversity that displayed potentialities in biological research. A considerable number of these molecular architectures had been recorded from marine sponges belonging to different marine genera, including , , , , and New Caledonian starfishes and . In this review, we aim to comprehensively cover the chemodiversity and the bioactivities landmarks centered around the chemical constituents exclusively isolated from these three marine genera including , and over the period 1981-2017, paying a special attention to the polycyclic guanidinic compounds and their proposed biomimetic landmarks.

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.

Unguiculin A and Ptilomycalins E-H, Antimalarial Guanidine Alkaloids from the Marine Sponge Monanchora unguiculata.

Chemical study of the CHCl-MeOH (1:1) extract from the sponge Monanchora unguiculata collected in Madagascar highlighted five new compounds, one acyclic guanidine alkaloid, unguiculin A (1) and four pentacyclic alkaloids, ptilomycalins E-H (2-5), along with four known compounds: crambescidin 800 (6) and crambescidin 359 (7), crambescidic acid (8), and fromiamycalin (9). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity.

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.

Remarkably high homoselectivity in [2 + 2] photodimerization of trans-cinnamic acids in multicomponent systems.

[2 + 2] homoadducts were exclusively obtained with total regio- and stereo-selectivities when a suspension of several solid photoactive trans-cinnamic acids in cyclohexane was stirred and irradiated.

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.

Molecular Iodine-Catalyzed Aerobic α,β-Diamination of Cyclohexanones with 2-Aminopyrimidine and 2-Aminopyridines.

Molecular iodine is shown to be an excellent catalyst for aerobic oxidative α,β-diamination of cyclohexanones with 2-aminopyrimidine/2-aminopyridines. This α,β-C-H functionalization is remarkable for its simplicity in both substrates and conditions, involving one and a half oxygen molecules and releasing three water molecules as the only byproduct. In addition, the functionalized products including protected 2-aminoimidazoles introduced without aromatization can serve as useful building blocks for natural product synthesis and medicinal chemistry.

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.

Elements as Direct Feedstocks for Organic Synthesis: Fe/I2/O2 for Diamination of 2-Cyclohexenones with 2-Aminopyrimidine and 2-Aminopyridines.

Elements as feedstocks for organic synthesis, the trio of metallic iron, molecular iodine, and dioxygen, were found to be an excellent tool for oxidative regioselective diamination of conjugated enones with 2-aminopyrimidine (a guanidine surrogate) and 2-aminopyridines leading to unaromatized coupled products in moderate to good yields.