Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis

Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines.     

Polyunsaturated Aldehydes from Large Phytoplankton of the Atlantic Ocean Surface (42°N to 33°S)

Polyunsaturated aldehydes (PUAs) are organic compounds mainly produced by diatoms, after cell wounding. These compounds are increasingly reported as teratogenic for species of grazers and deleterious for phytoplanktonic species, but there is still scarce information regarding concentration ranges and the composition of PUAs in the open ocean. In this study, we analyzed the spatial distribution and the type of aldehydes produced by the large-sized (>10 μm) phytoplankton in the Atlantic Ocean surface. Analyses were conducted on PUAs released after mechanical disruption of the phytoplankton cells, referred to here as potential PUAs (pPUAs). Results show the ubiquitous presence of pPUA in the open ocean, including upwelling areas, as well as oligotrophic gyres. Total pPUA concentrations ranged from zero to 4.18 pmol from cells in 1 L. Identified PUAs were heptadienal, octadienal and decadienal, with heptadienal being the most common (79% of total stations). PUA amount and composition across the Atlantic Ocean was mainly related to the nitrogen:phosphorus ratio, suggesting nutrient-driven mechanisms of PUA production. Extending the range of trophic conditions considered by adding data reported for productive coastal waters, we found a pattern of PUA variation in relation to trophic status.     

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.     

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development.     

Phosphorus fractions and their availability in the sediments of eight tropical semiarid reservoirs

Journal of Soils and Sediments - We quantified the phosphorus (P) fractions and oxide content in the sediment of eight tropical semiarid reservoirs to assess how water-level decreases affect the...     

A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil

The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.     

Tuberculosis survey of free-ranging marsh deer (Blastocerus dichotomus) in Brazil.

Esophageal-pharyngeal fluids from 53 free-ranging marsh deer (Blastocerus dichotomus) captured for a research program in the state of Mato Grosso do Sul, Brazil, were assayed for tuberculosis. Total DNA was extracted. amplified by polymerase chain reaction using specific primers for Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. microti, and M. africanum), and observed by agarose gel electrophoresis stained with ethidium bromide. All samples were negative. This, along with necropsy and histopathology data, suggests that these animals are not shedding and probably do not have active disease.     

An immunohistochemical study of the tonsils in pigs with acute African swine fever virus infection

An immunohistochemical study of the tonsils was carried out to gain further insight in the pathogenesis of acute African swine fever (ASF). Twenty-one pigs were inoculated by intramuscular route with a highly virulent isolate of ASF virus and painlessly killed at 1-7dpi. Viral antigen was highly distributed in the tonsil from 3 to 4dpi and an increase in the number of monocyte-macrophages was very evident at the same days post inoculation. This phenomenon was observed together with an increase of the expression of proinflammatory cytokines (Tumour necrosis factor alpha and Interleukin-1 alpha) and the apoptosis of lymphocytes studied by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) technique and haemorrhages. With these results, we can conclude that the tonsil is suffering similar lesions than those observed in other lymphoid organs in acute African swine fever, even when the route of inoculation is the intramuscular and not oral-nasal.     

Direct and indirect detection of 2n eggs in hybrid diploid families derived from haploid tbr × wild species crosses

The analytic-synthetic scheme makes use of haploidization and 2n gametes-mediated sexual polyploidization to incorporate genetic diversity from wild related species in potato breeding. Whereas 2n pollen can be directly screened by microscopy, 2n eggs are routinely screened indirectly by interploid crosses, a time-consuming and inaccurate technique. In five haploid tbr × wild diploid species families with variability for agronomic characters, 2n eggs were screened indirectly to incorporate this germplasm into a useful form and directly by microscopy to establish the feasibility of this approach. For the indirect screening, at least 15 flowers of each of 49 genotypes/family were crossed with a commercial cultivar. Eighty-five fruits were produced; only 15 of them had seeds (1–25). Chromosome numbers were determined in a random sample of five seeds/fruit, resulting diploid in two genotypic combinations and tetraploid in another two. For the direct screening, eight combinations of staining and destaining (times and concentrations) were evaluated in detached ovules to adjust a clarification technique. The best combination was one day of staining and one day of destaining in 0.5 % acetic acid. In an indirectly detected diplogynoid, the average diameters of the central cell nuclei (CCN) and nucleoli (CCNu) were, respectively, 9.3 μ and 3.4 μ. Gametophytes with diametres 1.26 times the average were considered 2n. By crosses, eleven seeds were obtained in one fruit of this clone whereas the 2n egg frequency determined by microscopy was 7%. The direct technique is easy to carry out once the eye is trained and its results better reflect actual 2n gamete frequencies.