A new kaurane diterpene dimer from Parinari campestris

A new kaurane diterpene dimer, 15-oxozoapatlin-13alpha-yl-10'alpha,16'alpha-dihydroxy-9'alpha-methyl-20'-nor-kauran-19'-oic acid gamma-lactone-17'-oate (1), together with the known 13-hydroxy-15-oxozoapatlin (2), 10alpha,13alpha,16alpha,17-tetrahydroxy-9alpha-methyl-15-oxo-20-nor-kauran-19-oic acid gamma-lactone (3), 2alpha,10alpha,13alpha,16alpha,17-pentahydroxy-9alpha-methyl-15-oxo-20-nor-kauran-19-oic acid (19,10)-lactone (4), 3alpha,10alpha,13alpha,16alpha,17-pentahydroxy-9alpha-methyl-15-oxo-20-nor-kauran-19-oic acid gamma-lactone (5), and 1beta,16alpha,17-trihydroxy-ent-kaurane (6) were isolated from the leaves of Parinari campestris and identified on the basis of detailed spectral analysis, including 2D NMR spectrometry and ESI-MS.     

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga,Dictyota menstrualis

Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines.     

Antitumor and Antimicrobial Potential of Bromoditerpenes Isolated from the Red Alga,Sphaerococcus coronopifolius

Cancer and infectious diseases continue to be a major public health problem, and new drugs are necessary. As marine organisms are well known to provide a wide range of original compounds, the aim of this study was to investigate the bioactivity of the main constituents of the cosmopolitan red alga, Sphaerococcus coronopifolius. The structure of several bromoditerpenes was determined by extensive spectroscopic analysis and comparison with literature data. Five molecules were isolated and characterized which include a new brominated diterpene belonging to the rare dactylomelane family and named sphaerodactylomelol (1), along with four already known sphaerane bromoditerpenes (2–5). Antitumor activity was assessed by cytotoxicity and anti-proliferative assays on an in vitro model of human hepatocellular carcinoma (HepG-2 cells). Antimicrobial activity was evaluated against four pathogenic microorganisms: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compound 4 exhibited the highest antimicrobial activity against S. aureus (IC₅₀ 6.35 µM) and compound 5 the highest anti-proliferative activity on HepG-2 cells (IC₅₀ 42.9 µM). The new diterpene, sphaerodactylomelol (1), induced inhibition of cell proliferation (IC₅₀ 280 µM) and cytotoxicity (IC₅₀ 720 µM) on HepG-2 cells and showed antimicrobial activity against S. aureus (IC₅₀ 96.3 µM).     

Antimicrobial ent-pimarane diterpenes from Viguiera arenaria against Gram-positive bacteria

The dichloromethane crude extract from the roots of Viguiera arenaria (VaDRE) has been employed in an antimicrobial screening against several bacteria responsible for human pathologies. The main diterpenes isolated from this extract, as well as two semi-synthetic pimarane derivatives, were also investigated for the pathogens that were significantly inhibited by the extract (MIC values lower than 100 μg mL^− 1). The VaDRE extract was significantly active only against Gram-positive microorganisms. The compounds ent-pimara-8(14),15-dien-19-oic acid (PA); PA sodium salt; ent-8(14),15-pimaradien-3β-ol; ent-15-pimarene-8β,19-diol; and ent-8(14),15-pimaradien-3β-acetoxy displayed the highest antibacterial activities (MIC values lower than 10 μg mL^− 1 for most pathogens). In conclusion, our results suggest that pimaranes are an important class of natural products for further investigations in the search of new antibacterial agents.     

neo-Clerodane diterpenes from Ajuga decumbens and their inhibitory activities on LPS-induced NO production

A phytochemical investigation of the whole plants of Ajuga decumbens led to the isolation of three new (1, 2a, and 2b) and three known (3a−3c) neo-clerodane diterpenes. Their structures were elucidated by spectroscopic data analysis (IR, ESIMS, HR-ESIMS, 1D and 2D NMR), and the structure of 1 was confirmed by X-ray crystallography. The inhibitory activities on LPS-induced NO production of the six diterpenes were evaluated and compounds 2a, 2b, and 3a showed inhibitory effects.     

Molluscicidal and anti-feedant activities of diterpenes from Euphorbia paralias L

Nine known diterpene polyesters of segetanes, jatrophenes and paralianes have been isolated from the aerial parts of Euphorbia paralias L. The molluscicidal activity of isolated compounds was evaluated on Biomphalaria alexandrina (Ehrenberg). Paraliane diterpene, (2S,3S,4R,5R,6R,8R,12S,13S,14R,15R)-5,8,14-triacetoxy-3-benzoyloxy-15- hydroxy-9-oxo-paraliane, was the most potent compound against the snail. Anti-feedant activity was tested by a conventional leaf disc method against third-instar larvae of Spodoptera littoralis (Boisd). Jatrophene diterpene, (2R,3R,4S,5R,7S,8R,13R,15R)-2,3,5,7,15-pentaacetoxy-8-angeloyloxy-14,15- dioxojatropha-6(17)-11E-diene, had the highest anti-feedant activity among the compounds tested.     

Ionic interactions and salinity affect monoterpene and phenolic diterpene composition in rosemary (Rosmarinus officinalis)

In this study, we evaluated how increased cation supply can alleviate the toxic effects of NaCl on plants and how it affects essential oils (EOs) and phenolic diterpene composition in leaves of rosemary (Rosmarinus officinalis L.) plants grown in pots. Two concentrations of the chloride salts KCl, CaCl₂, MgCl₂, and FeCl₃ were used together with 100 mM NaCl to study the effects of these nutrients on plant mineral nutrition and leaf monoterpene, phenolic diterpene, and EO composition. The addition of 100 mM NaCl, which decreased K⁺, Ca²⁺, and Mg²⁺ concentrations with increasing Na⁺ in leaves, significantly altered secondary metabolite accumulation. Addition of MgCl₂ and FeCl₃ altered leaf EO composition in 100 mM NaCl–treated rosemary plants while KCl and CaCl₂ did not. Furthermore, addition of CaCl₂ promoted the accumulation of the major phenolic diterpene, carnosic acid, in the leaves. The carnosol concentration was reduced by the addition of KCl to salt‐stressed plants. It is concluded that different salt applications in combination with NaCl treatment may have a pronounced effect on phenolic diterpene and EO composition in rosemary leaves thus indicating that ionic interactions may be carefully considered in the cultivation of these species to achieve the desired concentrations of these secondary metabolites.     

The Prospective Use of Brazilian Marine Macroalgae in Schistosomiasis Control

Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC–MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.     

Scopararanes C-G: new oxygenated pimarane diterpenes from the marine sediment-derived fungus Eutypella scoparia FS26

Five new oxygenated pimarane diterpenes, named scopararanes C-G (1-5) were isolated from the culture of a marine sediment-derived fungus Eutypella scoparia FS26 obtained from the South China Sea. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The absolute configurations of compounds 1-5, were determined by CD spectroscopic analysis and comparison with literature data. All isolated compounds (1-5) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method.