Chemical and biological studies on the soft coral Nephthea sp.

Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti-proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n-butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC50 values of 2.30 ± 0.07 and 3.12 ± 0.10 µg ml-1, respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC50 = 2.78 ± 0.09 µg ml-1). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC50 values of 0.72 ± 0.06 and 9.32 ± 0.57 µg ml-1, respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Both ethyl acetate and aqueous fractions of Tabebuia aurea leaves exhibited noteworthy antioxidant and nephroprotective activities against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, as evidenced by the remarkable improvements of renal serum biomarkers and histopathological features. Additionally, the ethyl acetate fraction displayed a prominent in vitro antitrypanosomal activity against Trypanosoma brucei; consequently, the leaves were subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, ten metabolites were characterized, mostly dominated by flavonoids. Interestingly, two identified constituents viz., 3,9,12,15-octadecatetraenoic acid (9) and 9,11,13-octadecatrienoic acid (10) are reported firstly herein from the genus Tabebuia. Furthermore, among the dereplicated constituents, rutin (5) and kaempferol 3-O-rutinoside (6) exhibited the highest docking scores as effective antitrypanosomal compounds.

Natural Products Repertoire of the Red Sea.

Marine natural products have achieved great success as an important source of new lead compounds for drug discovery. The Red Sea provides enormous diversity on the biological scale in all domains of life including micro- and macro-organisms. In this review, which covers the literature to the end of 2019, we summarize the diversity of bioactive secondary metabolites derived from Red Sea micro- and macro-organisms, and discuss their biological potential whenever applicable. Moreover, the diversity of the Red Sea organisms is highlighted as well as their genomic potential. This review is a comprehensive study that compares the natural products recovered from the Red Sea in terms of ecological role and pharmacological activities.

Metabolomics analysis and biological investigation of three Malvaceae plants.

INTRODUCTION: Metabolomics is a fast growing technology that has effectively contributed to many plant-related sciences and drug discovery. OBJECTIVE: To use the non-targeted metabolomics approach to investigate the chemical profiles of three Malvaceae plants, namely Hibiscus mutabilis L. (Changing rose), H. schizopetalus (Dyer) Hook.f. (Coral Hibiscus), and Malvaviscus arboreus Cav. (Sleeping Hibiscus), along with evaluating their antioxidant and anti-infective potential. METHODOLOGY: Metabolic profiling was carried out using liquid chromatography coupled with high-resolution electrospray ionisation mass spectrometry (LC-HR-ESI-MS) for dereplication purposes. The chemical composition of the studied plants was further compared by principal component analysis (PCA). The antioxidant and anti-infective properties of their different extracts were correlated to their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS: A variety of structurally different metabolites, mostly phenolics, were characterized. Comparing the distribution pattern of these tentatively identified metabolites among the studied plant species/fractions revealed the chemical uniqueness of the dichloromethane fraction of M. arboreus. Some extracts and fractions of these plants demonstrated noteworthy antioxidant and antitrypanosomal potential; the latter was partly attributed to their anti-protease activities. The active principles of these plants were pinpointed before any laborious isolation steps, to avoid the redundant isolation of previously known compounds. CONCLUSION: This study highlighted the use of the established procedure in exploring the metabolomes of these species, which could be helpful for chemotaxonomic and authentication purposes, and might expand the basis for their future phytochemical analysis. Coupling the observed biological potential with LC-MS data has also accelerated the tracing of their bioactive principles.

A new antitrypanosomal alkaloid from the Red Sea marine sponge Hyrtios sp.

The antitrypanosomally active crude extract of the sponge Hyrtios sp. was subjected to metabolomic analysis using liquid chromatography coupled with high resolution electrospray ionization mass spectrometry (LC-HR-ESIMS) for dereplication purposes. As a result, a new alkaloid, hyrtiodoline A (1), along with other four known compounds (2-5) were reported. The structures of compounds 1-5 were determined by spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESI-MS) experiments, as well as comparison to the literature. We further investigated the antitrypanosomal activity of the five compounds, where compound 1 exhibited the most potent antitrypanosomal activity, with a half-maximal inhibitory concentration (IC50) value of 7.48 µM after 72 h.

Chemical perturbation of secondary metabolism demonstrates important links to primary metabolism.

Bacterially produced secondary metabolites are used as antibiotics, anticancer drugs, and for many other medicinal applications. The mechanisms that limit the production of these molecules in the laboratory are not well understood, and this has impeded the discovery of many important compounds. We have identified small molecules that remodel the yields of secondary metabolites in many actinomycetes and show that one set of these molecules does so by inhibiting fatty acid biosynthesis. This demonstrates a particularly intimate relationship between this primary metabolic pathway and secondary metabolism and suggests an approach to enhance the yields of metabolites for discovery and biochemical characterization.

Diversity of nonribosomal peptide synthetase genes in the microbial metagenomes of marine sponges.

Genomic mining revealed one major nonribosomal peptide synthetase (NRPS) phylogenetic cluster in 12 marine sponge species, one ascidian, an actinobacterial isolate and seawater. Phylogenetic analysis predicts its taxonomic affiliation to the actinomycetes and hydroxy-phenyl-glycine as a likely substrate. Additionally, a phylogenetically distinct NRPS gene cluster was discovered in the microbial metagenome of the sponge Aplysina aerophoba, which shows highest similarities to NRPS genes that were previously assigned, by ways of single cell genomics, to a Chloroflexi sponge symbiont. Genomic mining studies such as the one presented here for NRPS genes, contribute to on-going efforts to characterize the genomic potential of sponge-associated microbiota for secondary metabolite biosynthesis.

Anti-parasitic compounds from Streptomyces sp. strains isolated from Mediterranean sponges.

Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC(50) < 0.11 microM; staurosporine IC(50) 5.30 microM) and Trypanosoma brucei brucei (valinomycin IC(50) 0.0032 microM; staurosporine IC(50) 0.022 microM; butenolide IC(50) 31.77 microM). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities.

Streptomyces axinellae sp. nov., isolated from the Mediterranean sponge Axinella polypoides (Porifera).

An actinomycete strain, isolated from the marine sponge Axinella polypoides collected from Banyuls-sur-Mer, France, was characterized using a polyphasic approach. Based on its chemotaxonomic and morphological characteristics, strain Pol001(T) belongs to the genus Streptomyces. The strain is characterized by ll-diaminopimelic acid in the cell wall, menaquinones MK-9(H(4), H(6), H(8)) and a DNA G+C content of 71.0 mol%. It forms a separate phyletic line based on phylogenetic analyses of the nearly complete 16S rRNA gene sequence. Strain Pol001(T) could be differentiated from other closely related Streptomyces species with validly published names by phenotypic and genotypic analysis. DNA-DNA hybridization between strain Pol001(T) and closely related reference strains further confirmed that strain Pol001(T) represents a novel taxon of the genus Streptomyces. Therefore, it is proposed that strain Pol001(T) represents a novel species in the genus Streptomyces, Streptomyces axinellae sp. nov.; the type strain is Pol001(T) (=DSM 41948(T) =CIP 109838(T)).

Saccharopolyspora cebuensis sp. nov., a novel actinomycete isolated from a Philippine sponge (Porifera).

The taxonomic status of a marine actinomycete isolated from the sponge Haliclona sp. collected from Cebu, Philippines, was established using both phenotypic and genotypic data. Strain SPE 10-1(T) exhibited chemotaxonomic and morphological characteristics that were consistent with those of members of the genus Saccharopolyspora. It showed a strict requirement for salt and is the first obligate marine bacterium of the genus Saccharopolyspora to be isolated. The principal isoprenoid quinone detected was MK-9(H(4)). The fatty acid pattern consisted mainly of terminally branched iso and anteiso fatty acids. The DNA G+C content was 72.6 mol%. Analysis of the 16S rRNA gene sequence supported affiliation of the strain with the genus Saccharopolyspora; the type strain of Saccharopolyspora gregorii was the closest phylogenetic relative (96 % sequence similarity). Sequence similarities of strain SPE 10-1(T) to other type strains of this genus were 93-95 %. It is proposed that strain SPE 10-1(T) should be classified in the genus Saccharopolyspora as a representative of Saccharopolyspora cebuensis sp. nov. The type strain of Saccharopolyspora cebuensis is SPE 10-1(T) (=DSM 45019(T)=CIP 109355(T)).