Marine Drugs最新文献

Although the density and diversity of seaweeds in Madagascar is particularly high, these resources are underexploited and they are not part of the local population's eating habits. No study has been carried out on the nutritional properties and seasonal variation of Eucheuma species harvested in Madagascar. In this study, Eucheuma denticulatum was harvested monthly over two years (2021 and 2022) on the northeast coast of Madagascar (Sainte Marie Island). The compositional analysis revealed prominent sugars and minerals up to 41.0 and 39.5% dw, respectively. E. denticulatum showed slight variability over the seasons in the macroelements and oligoelements (Ca, K, Na, Mg, Fe, Mn) ranging from 22.8 ± 0.2 to 25.3 ± 0.1% dw in 2021 and 22.1 ± 0.3 to 26.5 ± 0.3% dw in 2022. Total amino acids varied from 2.3 ± 0.6 to 2.5 ± 0.6% dw during the two years. Seaweed extracts showed antioxidant activity by the in vitro method ranging from 2026 ± 2 to 2998 ± 4 μg.mL^-1 in 2021, and from 1904 ± 2 to 2876 ± 4 μg.mL^-1 in 2022. Finally, the principal component analysis (PCA) showed a correlation between protein content and environmental parameters. The nutritional characteristics therefore confirmed that E. denticulatum could potentially be used as a nutritious and functional food and could be incorporated in the diet of local populations.

Heavy chain-only antibodies in sharks are called immunoglobulin new antigen receptors (IgNAR), consisting of one variable region (VNAR) and five constant regions (C1-C5). The variable region of IgNAR can be expressed as a monomer composed of a single domain, which has antigen specificity and is thus gaining attention as a next-generation antibody drug modality. In this study, we analyzed IgNAR of the cloudy catshark and Japanese bullhead shark, small demersal sharks available in the coastal waters of Japan. By analyzing the IgNAR gene sequence and comparing it with the constant regions of five other known shark species, high homology was observed in the C4 region. Consequently, we expressed the recombinant protein of the C4 domain from the cloudy catshark in E. coli, immunized rats, and produced antibodies. The obtained antiserum and mAbs recognized the C4 recombinant protein of the cloudy catshark, but reacted minimally with the plasma of non-immunized cloudy catsharks and instead reacted with the plasma of Japanese bullhead sharks. The results of this study imply that the protein expression levels of IgNAR in cloudy catsharks may be relatively lower compared to those in Japanese bullhead sharks, however, this interpretation remains to be determined through further studies.

Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, the capsular polysaccharide (CPS) was obtained from the bacterium Cobetia marina KMM 1449, isolated from a marine sediment sample collected along the shore of the Sea of Japan. The CPS was isolated by saline solution, purified by a series of chromatographic procedures, and studied by chemical methods along with 1D and 2D ¹H and ¹³C NMR spectroscopy. The following new structure of the CPS from C. marina KMM 1449 was established and consisted of sulfated and simultaneously phosphorylated disaccharide repeating units: →4)-α-L-Rhap2S-(1→3)-β-D-Manp6PGro-(1→. To elucidate the genetic basis of the CPS biosynthesis, the whole genomic sequence of C. marina KMM 1449 was obtained. The CPS biosynthetic gene cluster (BGC) of about 70 genes composes four regions encoding nucleotide sugar biosynthesis (dTDP-Rha and GDP-Man), assembly (GTs genes), translocation (ABC transporter genes), sulfation (PAPS biosynthesis and sulfotransferase genes) and lipid carrier biosynthesis (wcb operon). Comparative analysis of the CPS BGCs from available Cobetia genomes showed the presence of KMM 1449-like CPS BGC among strains of all three Cobetia species. The study of new natural sulfated polysaccharides, as well as the elucidation of the pathways of their biosynthesis, provides the basis for the development of potential anticancer drugs.

The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h. Our results demonstrated that all of the toxins could impair barrier integrity after 24 h, with differences observed for PnTX-A, -E, and -F, as well as portimine, the most potent of all. While PnTX-A and -E exhibited poor permeability, the other PnTXs were more penetrative, with a Papp > 1.5 × 10^-6 cm·s^-1. Portimine was the only toxin displaying both a time- and concentration-dependent passage, likely involving a passive diffusion process. The experimental results were compared to predictions obtained by QSAR tools. Although only qualitative, our results suggest that some of these compounds may be more likely to be distributed throughout the body. Further in vivo studies are required to estimate oral bioavailability and potential public health concerns.

Fucoidan is a sulfated polysaccharide found in brown seaweed. Due to its reported biological activities, including antiviral, antibacterial and anti-inflammatory activities, it has garnered significant attention for potential biomedical applications. However, the direct relationship between fucoidan extracts' chemical structures and bioactivities is unclear, making it extremely challenging to predict whether an extract will possess a given bioactivity. This relationship is further complicated by a lack of uniformity in the recent literature in terms of the assessment and reporting of extract properties, yield and chemical composition (e.g., sulfate, fucose, uronic acid and monosaccharide contents). These inconsistencies pose significant challenges when directly comparing extraction techniques across studies. This review collected data on extract contents and properties from a selection of available studies. Where information was unavailable directly, efforts were made to extrapolate data. This approach enabled a comprehensive examination of the correlation between extraction techniques and the characteristics of the resulting extracts. A holistic framework is presented for the selection of fucoidan extraction methods, outlining key heuristics to consider when capturing the broader context of a seaweed bioprocess. Future work should focus on developing knowledge within these heuristic categories, such as the creation of technoeconomic models of each extraction process. This framework should allow for a robust extraction selection process that integrates process scale, cost and constraints into decision making. Key quality attributes for biologically active fucoidan are proposed, and areas for future research are identified, such as studies for specific bioactivities aimed at elucidating fucoidan's mechanism of action. This review also sets out future work required to standardize the reporting of fucoidan extract data. Standardization could positively enhance the quality and depth of data on fucoidan extracts, enabling the relationships between physical, chemical and bioactive properties to be identified. Recommendations on best practices for the production of high-quality fucoidan with desirable yield, characteristics and bioactivity are highlighted.

LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. Six compounds were optimized for protein binding after being docked against the positive control Compound A. Two compounds showed promising results in ADMET screening. Molecular dynamics simulations were utilized to predict binding mechanisms, with Compound 69081_50 identified as a potential LCN2 inhibitor. MM-PBSA analysis revealed key amino acid residues that are involved in interactions, suggesting that Compound 69081_50 could be a candidate for drug development.

Angucyclines/angucyclinones, a class of polyketides with diverse chemical structures, display various bioactivities including antibacterial or antifungal, anticancer, anti-neuroinflammatory, and anti-α-glucosidase activities. Marine and terrestrial microorganisms have made significant contributions to the discovery of bioactive angucyclines/angucyclinones. This review covers 283 bioactive angucyclines/angucyclinones discovered from 1965 to 2023, and the emphasis is on the biological origins, chemical structures, and biological activities of these interesting natural products.

Filoviruses, mainly consisting of the two genera of Ebolavirus and Marburgvirus, are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these diseases. To search for effective drugs, we have identified three marine indole alkaloids that exhibit potent activities against filovirus infection. Thus, it is suggested that marine indole alkaloids can be a valuable compound source for filovirus drug screening and development. Since marine indole alkaloids comprise a large diverse group of secondary metabolites, their biological properties would be helpful for pharmaceutical drug development to treat various filovirus infections.

Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid oil using immobilized lipase (Lipozyme RMIM) was demonstrated, resulting in high acylglyceride yields. The processed oil was analyzed for oxidation kinetics and thermodynamics using Rancimat, fatty acid composition using GC, omega-3 fatty acid positional distribution in the acylglyceride product using ¹³C NMR, and astaxanthin content. Lipase treatment reduced FFA levels from 44% to 4% and increased acylglycerides to 93% in squid oil. This reduction in FFA was accompanied by significantly increased stability (0.06 to 18.9 h by Rancimat). The treated oil showed no loss in astaxanthin (194.1 µg/g) or omega-3 fatty acids, including docosahexaenoic acid (DHA). DHA remaining predominantly at sn-2 indicated that the naturally occurring positional distribution of this omega-3 FFA was retained in the product. Lipase treatment significantly enhanced oxidative stability, evidenced by improved thermodynamic parameters (E_a 94.15 kJ/mol, ΔH 91.09 kJ/mol, ΔS -12.6 J/mol K) and extended shelf life (IP₂₅ 74.42 days) compared to starting squid oil and commercial fish/squid oils lacking astaxanthin. Thus, lipase treatment offers an effective strategy for reducing FFA levels and producing oxidatively stable, astaxanthin-rich acylglyceride squid oil with DHA retained at the nutritionally favored sn-2 position.

Matteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The "classical version" allows the introduction of various functional groups in a 1,2-anti-configuration. The absolute configuration is determined by the choice of the chiral auxiliary, which can be used to introduce several stereogenic centers. In contrast, in Aggarwal's lithiation-borylation strategy, new chiral auxiliary reagents must be used in each reaction step, which on the other hand allows the individual insertion of the desired stereogenic centers. Both methods have their individual advantages and disadvantages and are well suited for the synthesis of marine natural products.