Non-Cytotoxic Sulfated Heterorhamnan from Gayralia brasiliensis Green Seaweed Reduces Driver Features of Melanoma Metastatic Progression.

Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

NMR and rheological study of Aloe barbadensis partially acetylated glucomannan.

The structural and rheological properties of the Aloe extract (AE) and the polysaccharidic fraction (PF) obtained from the leaves pulp of Aloe barbadensis Miller were investigated. Structural analyses carried out by composition, methylation analysis and NMR spectroscopy showed that PF is mainly constituted by a partially acetylated 4-linked ß-d-glucomannan. The acetyl groups are located at C-2, C-2 and C-3, C-3 and/or C-6. The acetylation pattern of this type of polysaccharide was for the first time established using bidimensional NMR analyses. AE and PF aqueous solutions at 25°C showed a non-Newtonian behavior (with pseudoplastic characteristics), however PF showed higher apparent viscosity than AE. Dynamic oscillatory analyses showed that both samples, at the same concentration, behaved as a concentrated solution. PF presented higher values of G' compared with those of AE and this behavior could be consequence of its higher content in partially acetylated glucomannan.

Semisynthesis of long-chain alkyl ether derivatives of sulfated oligosaccharides via dibutylstannylene acetal intermediates.

Long-chain alkyl ether derivatives of sulfated oligosaccharides were semisynthesized as follows: two naturally occurring red seaweed galactans (neutral agarose and kappa-carrageenan) were submitted to partial reductive hydrolysis to give neutral and sulfated oligosaccharide alditols. The neutral disaccharide alditol (1) and its trityl ether (5) were sulfated and/or alkylated through formation of their dibutylstannylene or (bis)dibutylstannylene acetals. In these reactions, the dibutylstannylene acetals of the terminal 1,2-diols in the alditol units were more reactive than those formed on the cis-diols of the galactopyranosidic units. This property allowed the regioselective monoalkylation of a neutral tetrasaccharide alditol (2), which contained eleven free hydroxyl groups, the highest selectivity ever observed with dibutylstannylene acetals. An alkylated/sulfated derivative (11) was also obtained through the regioselective alkylation of a naturally sulfated disaccharide alditol (10, a kappa-carrageenan derivative).

Regioselective synthesis of long-chain ethers and their sulfates derived from methyl beta-D-galactopyranoside and derivatives via dibutylstannylene acetal intermediates.

A number of different conditions were investigated for the alkylation of the dibutylstannylene acetals of methyl beta-d-galactopyranoside with long-chain primary alkyl bromides, decyl, dodecyl, and tetradecyl bromide. The best yields of the major products, the 3-O-alkyl ethers, were obtained by reaction of the alkyl bromide with the monodibutylstannylene acetal in DMF in the presence of cesium fluoride for extended periods of time at moderate temperatures (65 degrees C). These products were always accompanied by minor amounts of the 3,6-di-O-alkyl derivative. Performing the reaction with excess alkyl halide on the bis(dibutylstannylene) acetal resulted in more of the 3,6-di-O-alkyl derivative, particularly for the shorter alkyl bromides, but this product was never predominant. Sulfation of the dibutylstannylene acetal of methyl 3-O-tetradecyl-beta-D-galactopyranoside resulted in the 6-sulfate in 96% yield.

The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell.

Two homogeneous sulfated polysaccharides obtained from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata, the kappa/iota/nu carrageenan G3d and the dl-galactan hybrid C2S-3, were assayed for their antiviral properties against the four serotypes of dengue virus (DENV) in different host cell types. Both seaweed derivatives were selective inhibitors of DENV-2 multiplication in Vero cells with inhibitory concentration 50% (IC50) values around 1 microg/ml and selectivity indices > 1000. The compounds had a lower antiviral effect against DENV-3 (IC50 values in the range 13.9-14.2 microg/ml), an even lower effect against DENV-4 (IC50 values in the range 29.3 to > 50 microg/ml) and were totally inactive against DENV-1. With respect to the host cell, the polysulfates were inhibitors of DENV-2 and DENV-3 in the human hepatoma HepG2 and foreskin PH cells, with similar antiviral effectiveness as in Vero cells, but were totally inactive in mosquito C6/36 HT cells. Mechanistic studies demonstrated that G3d and C2S-3 were active DENV-2 inhibitors only when added together with the virus or early after infection, and both initial processes of virus adsorption and internalization are the main targets of these compounds. Therefore, the variations in antiviral activity of the polysaccharides depending on the viral serotype and the host cell may be ascribed to differences in the virus-cell interaction leading to virus entry.