Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea.

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.

Widespread biosynthesis of 16-carbon terpenoids in bacteria.

Terpenoids are the most diverse group of specialized metabolites with numerous applications. Their biosynthesis is based on the five-carbon isoprene building block and, as a result, almost all terpenoids isolated to date are based on backbones that contain multiples of five carbon atoms. Intrigued by the discovery of an unusual bacterial terpenoid with a 16-carbon skeleton, here we investigate whether the biosynthesis of 16-carbon terpenoids is more widespread than this single example. We mine bacterial genomic information and identify potential C16 biosynthetic clusters in more than 700 sequenced genomes. We study selected clusters using a yeast synthetic biology platform and reveal that the encoded synthases produce at least 47 different noncanonical terpenoids. By thorough chemical analysis, we explain the structures of 13 C16 metabolites, most of which possess intricate highly strained bi- and tricyclic backbones. Our results unveil the existence of an extensive class of terpenoids in bacteria.

Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks.

Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C16 scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.

Healthspan improvement and anti-aggregation effects induced by a marine-derived structural proteasome activator.

Proteasome activation has been shown to promote cellular and organismal healthspan and to protect against aggregation-related conditions, such as Alzheimer's disease (AD). Various natural compounds have been described for their proteasome activating properties but scarce data exist on marine metabolites that often possess unique chemical structures, exhibiting pronounced bioactivities with novel mechanisms of action. In this study, we have identified for the first time a marine structural proteasome activator, namely (1R,3E,6R,7Z,11S,12S)-dolabella-3,7,18-trien-6,17-olide (DBTO). DBTO activates the 20S proteasome complex in cell-free assays but also in cellulo. Continuous supplementation of human primary fibroblasts with DBTO throughout their cellular lifespan confers an improved healthspan while ameliorated health status is also observed in wild type (wt) Caenorhabditis elegans (C. elegans) nematodes supplemented with DBTO. Furthermore, treatment of various AD nematode models, as well as of human cells of neuronal origin challenged with exogenously added Aß peptide, with DBTO results in enhanced protection against Aß-induced proteotoxicity. In total, our results reveal the first structural proteasome activator derived from the marine ecosystem and highlight its potential as a compound that might be used for healthspan maintenance and preventive strategies against proteinopathies, such as AD.

What Was Old Is New Again: The Pennate Diatom Haslea ostrearia (Gaillon) Simonsen in the Multi-Omic Age.

The marine pennate diatom Haslea ostrearia has long been known for its characteristic blue pigment marennine, which is responsible for the greening of invertebrate gills, a natural phenomenon of great importance for the oyster industry. For two centuries, this taxon was considered unique; however, the recent description of a new blue Haslea species revealed unsuspected biodiversity. Marennine-like pigments are natural blue dyes that display various biological activities-e.g., antibacterial, antioxidant and antiproliferative-with a great potential for applications in the food, feed, cosmetic and health industries. Regarding fundamental prospects, researchers use model organisms as standards to study cellular and physiological processes in other organisms, and there is a growing and crucial need for more, new and unconventional model organisms to better correspond to the diversity of the tree of life. The present work, thus, advocates for establishing H. ostrearia as a new model organism by presenting its pros and cons-i.e., the interesting aspects of this peculiar diatom (representative of benthic-epiphytic phytoplankton, with original behavior and chemodiversity, controlled sexual reproduction, fundamental and applied-oriented importance, reference genome, and transcriptome will soon be available); it will also present the difficulties encountered before this becomes a reality as it is for other diatom models (the genetics of the species in its infancy, the transformation feasibility to be explored, the routine methods needed to cryopreserve strains of interest).

What Socrates drank? Comparative chemical investigation of two Greek Conium taxa exhibiting diverse chemical profiles.

Conium divaricatum, even though exhibiting morphological differences in comparison to its congener of European origin Conium maculatum, is still considered a disputed taxon often referred to as a synonym of the latter. Herein, essential oils of various plant tissues from several populations of both taxa were comparatively investigated, showing distinct chemical profiles. In the case of C. divaricatum, the essential oils were dominated by hydrocarbon esters, among which the main constituents 4'-oxodecyl hexanoate, 4'-oxododecyl hexanoate and 4'-oxooctyl hexanoate were isolated and identified as undescribed natural products. In contrast, the essential oils of C. maculatum were dominated by hydrocarbon alkanes, alkenes and ketones, as well as the polyacetylene (Z)-falcarinol. Even though determination of the total alkaloids content and toxicity assessment against the crustacean Artemia salina did not reveal significant differences, the distinct chemical profiles and the morphological differences observed for both taxa, strongly support their distinction as separate species.

Antioxidant Potential of Pine Needles: A Systematic Study on the Essential Oils and Extracts of 46 Species of the Genus Pinus.

The antioxidant activity of the essential oils, as well as of the organic and hydroethanolic extracts, of the fresh needles of 54 pine taxa was evaluated using the peroxy-oxalate and luminol chemiluminescence assays. Among all evaluated essential oils, P. canariensis and P. attenuata displayed the highest levels of activity. P. contorta var. murrayana, followed by P. nigra var. caramanica, exhibited the highest antioxidant capacity among the organic extracts, while the most active hydroethanolic extract was that of P. nigra subsp. nigra. Based on the overall levels of activity, the latter taxon was selected for phytochemical analysis targeting the isolation of the bioactive constituents. As such, the organic extract of P. nigra subsp. nigra was subjected to chromatographic separations to yield 11 secondary metabolites (1-11) that were evaluated for their antioxidant activity. Nonetheless, the isolated compounds were found to be less active than the crude extract, thus suggesting the potential role of synergism.

Thuwalallenes A-E and Thuwalenynes A-C: New C15 Acetogenins with Anti-Inflammatory Activity from a Saudi Arabian Red Sea Laurencia sp.

Thuwalallenes A-E (1-3, 5 and 8) and thuwalenynes A-C (4, 6, 7), new C15 acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol (11) were isolated from the organic extract of a population of the red alga Laurencia sp., collected at Rose Reef off the village of Thuwal in the Red Sea waters of the Kingdom of Saudi Arabia. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data. Compounds 1-6, 8, 10 and 11 were evaluated for their anti-inflammatory activity by quantifying nitric oxide (NO) release in response to TLR4 stimulation in macrophages. Besides compound 4 that did not exhibit any activity, all other tested metabolites inhibited NO production from activated macrophages. Among them, thyrsiferol (10) and 23-acetylthyrsiferol (11) displayed activity with IC50 values in the low nM scale without cytotoxicity.

Algae metabolites: from in vitro growth inhibitory effects to promising anticancer activity.

Covering: 1957 to 2017 Algae constitute a heterogeneous group of eukaryotic photosynthetic organisms, mainly found in the marine environment. Algae produce numerous metabolites that help them cope with the harsh conditions of the marine environment. Because of their structural diversity and uniqueness, these molecules have recently gained a lot of interest for the identification of medicinally useful agents, including those with potential anticancer activities. In the current review, which is not a catalogue-based one, we first highlight the major biological events that lead to various types of cancer, including metastatic ones, to chemoresistance, thus to any types of current anticancer treatment relating to the use of chemotherapeutics. We then review algal metabolites for which scientific literature reports anticancer activity. Lastly, we focus on algal metabolites with promising anticancer activity based on their ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. Thus, we highlight compounds that have, among others, one or more of the following characteristics: selectivity in reducing the proliferation of cancer cells over normal ones, potential for killing cancer cells through non-apoptotic signaling pathways, ability to circumvent MDR-related efflux pumps, and activity in vivo in relevant pre-clinical models.

Chemical Composition of Juniperus phoenicea and J. drupacea Essential Oils and their Biological Effects in the Choriallantoic Membrane (CAM) Assay.

The aim of the present study was the chemical analysis of the essential oils from Juniperus phoenicea and J. drupacea female cones and evaluation of their biological effects. Fresh samples, collected in Greece, were subjected separately to hydrodistillation and the oils obtained analyzed by GC-FID and GC-MS. The oils Were assessed using the CAM (chorioallantoic membrane) assay to evaluate their anti-angiogenic potential and the lack of irritant effects in topical application. GC analysis showed that mainly quantitative differences among the samples were observed: limonene was the most abundant compound in J. drupacea (27.0%) compared with J. phoenicea oil (1.6%); the content of a-pinene was high in both essential oils (J. phoenicea 22.1%, J. drpacea 26.1%) followed by germacrene D (J. phoenicea 7.4%, J. drpacea 7.1%, respectively). Nevertheless, qualitative differences were also detected as the diterpene 4-epi-abietal was present in a considerable amount (13.2%) in J. phoenicea essential oil, but was not detected in J. drupacea oil. In the CAM assay, only J. phoenicea. essential oil evidenced a rather weak anti-angiogenic activity compared with the standard retinoic acid, but no irritant effect was observed for either essential oil suggesting their safety for topical application.

Chemical Composition and Larvicidal Activity of Greek Myrtle Essential Oils against Culex pipiens biotype molestus.

Fresh leaves of Myrtus communis collected from different localities in Greece, were subjected to hydrodistillation and the oils obtained were analyzed by GC-FID and GC-MS. The analyses showed mainly quantitative differences, with the monoterpenes myrtenyl acetate, α-pinene, 1,8-cineole, and linalool, along with limonene, dominating the majority of the analyzed Myrtle oils. The evaluation of the larvicidal activity of the samples against Culex pipiens biotype molestus mosquito showed that all tested samples exhibited moderate to weak toxicity, with cultivated M. communis subsp. communis oil being the most active.

Antimicrobial activity of the essential oil of Greek endemic Stachys spruneri and its main component, isoabienol.

The essential oils of Stachys spruneri Boiss. (sample A and sample B) were analyzed by GC and GC-MS. (+)-Isoabienol was the dominant component (49.5 and 48.2%, respectively of the total oils) among seventy-two identified constituents. Isoabienol was separated, purified by preparative thin-layer chromatography, and further identified by means ofphysicochemical and spectrometric analysis. The microbial growth inhibitory properties of the essential oil and its main metabolite, the labdane diterpene isoabienol, were determined using the broth microdilution method against eight laboratory strains of bacteria (Gram-positive: Staphylococcus aureus, S. epidermidis, Micrococcus luteus, Enterococcus faecalis, Bacillus subtilis, and Gram- negative: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and two strains of the yeast Candida albicans. Both essential oil and isoabienol showed considerable activity against all the microorganisms tested, with the isolated compound being most active.

Volatile constituents of different parts of Smyrnium olusatrum from Greece.

The essential oils from stems, leaves, inflorescences, and both unripe and ripe infructescences of Smyrnium olusatrum L. (Umbelliferae) collected in Greece were obtained by hydrodistillation and analyzed by GC-FID and GC-MS. Fifty-eight components were identified. Among the samples analyzed, the differences observed were mainly quantitative. All oils were characterized by the abundance of sesquiterpenes. The major components of the stem and leaf oils were furanoeremophil-1-one (54.3% and 28.7%, respectively) and curzerene (18.8%, 29.0%). The main constituents of the inflorescence oil were curzerene (38.1%), germacrone (20.2%) and furanoeremophil-1-one (20.0%), while those of the unripe and ripe infructescence oils were 1beta-acetoxy-furanoeudesm-4(15)-ene (22.1%, 30.8%) and curzerene (29.7%, 17.4%).