Synthesis and antimicrobial properties of guanidine-functionalized labdane type diterpenoids.

The occurrence of increased antibiotic resistance has reduced the availability of drugs effective in the control of infectious diseases, especially those caused by various combinations of bacteria and/or fungi that are often associated with poorer patient outcomes. In the hunt for novel antibiotics of interest to treat polymicrobial diseases, molecules bearing guanidine moieties have recently come to the fore in designing and optimizing antimicrobial agents. Due to their remarkable antibacterial and antifungal activities, labdane diterpenes are also attracting increasing interest in antimicrobial drug discovery.

An Alkaloid from a Highly Invasive Seaweed Increases the Voracity and Reproductive Output of a Model Fish Species.

The invasive macroalga has spread widely in the Mediterranean Sea, becoming a favorite food item for native fish for reasons yet unknown. By using a combination of behavioral, morphological, and molecular approaches, herein we provide evidence that the bisindole alkaloid caulerpin, a major secondary metabolite of , significantly increases food intake in the model fish , influencing the regulation of genes involved in the orexigenic pathway. In addition, we found that the compound improves fish reproductive performance by affecting the hypothalamus-pituitary-gonadal axis.

Chasing Chances in a Changing Sea.

Bioactive marine natural products (BMNPs) of interest for applications as drugs, antimicrobials, cosmetics, nutraceuticals, or antifoulants, are often present in traces in producer organisms and often occur in threatened or endangered species, or in organisms playing key ecological roles [...

Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models.

NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age-related regulation of NPY in the brain and foregut of the shortest- and longest-lived fish species, Nothobranchius furzeri and Danio rerio, respectively.

Aerophobin-1 from the Marine Sponge Modulates Osteogenesis in Zebrafish Larvae.

Longer life expectancy has led to an increase in efforts directed to the discovery of new healing agents for disorders related to aging, such as bone diseases. Harboring an incredible variety of bioactive metabolites, marine organisms are standing out as fruitful sources also in this therapeutic field. On the other hand, the in vivo zebrafish model has proven to be an excellent low-cost screening platform for the fast identification of molecules able to regulate bone development.

Caulerpin Mitigates -Induced Inflammation via Formyl Peptide Receptors.

The identification of novel strategies to control ()-associated chronic inflammation is, at present, a considerable challenge. Here, we attempt to combat this issue by modulating the innate immune response, targeting formyl peptide receptors (FPRs), G-protein coupled receptors that play key roles in both the regulation and the resolution of the innate inflammatory response. Specifically, we investigated, in vitro, whether Caulerpin-a bis-indole alkaloid isolated from algae of the genus -could act as a molecular antagonist scaffold of FPRs.

The chemical and chemo-ecological studies on Weizhou nudibranch Glossodoris atromarginata.

A detailed chemical investigation of the nudibranch Glossodoris atromarginata collected from Weizhou Island, South China Sea, yielded a new spongian-type diterpene 1, together with the four known-related compounds 2-5. The structure of the new compound 1 was elucidated by the detailed spectroscopic analysis, the comparison of the spectroscopic data with the known diterpene isoagatholactone, and the C chemical shift calculation. In addition, evidence for the absolute stereochemistry of the known compound 2 was, for the first time, provided by the application of time-dependent density functional theory electronic circular dichroism calculation.

Amphilectene Diterpene Isonitriles and Formamido Derivatives from the Hainan Nudibranch .

Terpene content of two distinct collections of the nudibranch from the South China Sea has been chemically analyzed. A series of amphilectene diterpenes, most likely of dietary origin, with isocyano and formamido functionalities have been isolated from both collections and spectroscopically characterized by an exhaustive nuclear magnetic resonance (NMR) analysis. Interestingly, the structural architecture of compounds - and with both 8,13- and 12,13- ring junctions is unprecedented in the amphilectene skeleton.

A new bis-γ-pyrone polypropionate of onchidiol family from marine pulmonate mollusk sp.

A new bis-γ-pyrone polypropionate, 4,16-di--onchidiol (), along with three known related compounds (-) were isolated from the marine pulmonate mollusk sp. The structure of compound was elucidated by extensive spectroscopic analysis and by comparison the NMR data with its stereoisomers -, whereas its absolute configuration was determined by the combination of X-ray diffraction analysis and TDDFT-ECD calculation. In bioassay, the isolated compounds exhibited broad cytotoxicity against several cancer cell lines with IC values ranging from 24.

Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest.

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)-a bioactive component of the green alga that has invaded the entire Mediterranean basin-is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays.

¹H NMR Spectroscopy and MVA to Evaluate the Effects of Caulerpin-Based Diet on Lipid Profiles.

The biological invasion of the green algae represents a serious scientific and public issue in the Mediterranean Sea, essentially due to strong modifications both to habitat structure and native benthic communities. Although alterations in health status and changes in flesh quality of some marine species (dietary exposed to ) have been observed, no studies on cause-effect relationships have been carried out. Here, for the first time, through a controlled feeding experiment followed by ¹H NMR Spectroscopy and multivariate analysis (PCA, OPLS-DA), we showed that caulerpin taken with diet is directly responsible of changes observed in metabolic profile of fish flesh, including alteration of lipid metabolism, in particular with a reduction of ω3 PUFA content.

The Suitability of Fishes as Models for Studying Appetitive Behavior in Vertebrates.

Fish have proven to be valuable models in the study of the endocrine control of appetite in response to peripheral signals of energetic and nutritional status. In parallel, a growing body of literature points to the importance of sensory experiences as factors affecting food choice in fish, with a special focus on visual and chemical signals allowing discrimination of potential foods within a 3D environment. Accordingly, waterborne compounds, such as monosaccharides or amino acids, are regarded as the main "olfactory" cues driving fish alimentary behavior.

Sarinfacetamides A and B, Nitrogenous Diterpenoids with Tricyclo[6.3.1.0]dodecane Scaffold from the South China Sea Soft Coral Sarcophyton infundibuliforme.

Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring an uncommon tricyclo[6.3.1.

In Silico Identification and Experimental Validation of Novel Anti-Alzheimer's Multitargeted Ligands from a Marine Source Featuring a "2-Aminoimidazole plus Aromatic Group" Scaffold.

Multitargeting or polypharmacological approaches, looking for single chemical entities retaining the ability to bind two or more molecular targets, are a potentially powerful strategy to fight complex, multifactorial pathologies. Unfortunately, the search for multiligand agents is challenging because only a small subset of molecules contained in molecular databases are bioactive and even fewer are active on a preselected set of multiple targets. However, collections of natural compounds feature a significantly higher fraction of bioactive molecules than synthetic ones.

Cryptic effects of biological invasions: Reduction of the aggressive behaviour of a native fish under the influence of an "invasive" biomolecule.

The invasive green alga Caulerpa cylindracea has become an important component of the diet of the Mediterranean white seabream Diplodus sargus. As a consequence of this "exotic diet", the algal bisindolic alkaloid caulerpin accumulates in the fish tissues. Although the compound shows structural similarity to endogenous indolamines that modulate animal behaviour, the potential impact of caulerpin on fish behaviour still remains unexplored.

Marine Terpenoid Diacylguanidines: Structure, Synthesis, and Biological Evaluation of Naturally Occurring Actinofide and Synthetic Analogues.

A new diacylguanidine, actinofide (1), has been isolated from the marine mollusk Actinocyclus papillatus. The structure, exhibiting a guanidine moiety acylated by two terpenoid acid units, has been established by spectroscopic methods and secured by synthesis. Following this, a series of structural analogues have been synthesized using the same procedure.

Sarcophytrols G - L, Novel Minor Metabolic Components from South China Sea Soft Coral Sarcophyton trocheliophorum Marenzeller.

Minor metabolic components, six new cembranoids sarcophytrols G - L (1 - 6) along with two known related analogues 7 and 8, were isolated from the South China Sea soft coral Sarcophyton trocheliophorum. Their structures were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, and ESI-MS) as well as comparison with literature data. As part of our ongoing research project for discovering bioactive substances from Chinese marine invertebrates, compounds 1 - 8 were tested for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of Type-II diabetes and obesity.

Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments.

Olfaction is considered a distance sense; hence, aquatic olfaction is thought to be mediated only by molecules dissolved in water. Here, we challenge this view by showing that shrimp and fish can recognize the presence of hydrophobic olfactory cues by a "tactile" form of chemoreception. We found that odiferous furanosesquiterpenes protect both the Mediterranean octocoral and its specialist predator, the nudibranch gastropod , from potential predators.

Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance.

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as "chemotaxonomic markers" for the different molluscan species.

In Vitro Growth Inhibitory Activities of Natural Products from Irciniid Sponges against Cancer Cells: A Comparative Study.

Marine sponges of the Irciniidae family contain both bioactive furanosesterterpene tetronic acids (FTAs) and prenylated hydroquinones (PHQs). Both classes of compounds are known for their anti-inflammatory, antioxidant, and antimicrobial properties and known to display growth inhibitory effects against various human tumor cell lines. However, the different experimental conditions of the reported in vitro bioassays, carried out on different cancer cell lines within separate studies, prevent realistic actual discrimination between the two classes of compounds from being carried out in terms of growth inhibitory effects.