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The macrocyclic tumonolide (1) with enamide functionality and the linear tumonolide aldehyde (2) are new interconverting natural products from a marine cyanobacterium with a peptide‐polyketide skeleton, representing a hybrid of apratoxins and palmyrolides or laingolides. The planar structures were established by NMR and mass spectrometry. The relative configuration of the stereogenically‐rich apratoxin‐like polyketide portion was determined using J‐based configuration analysis. The absolute configuration of tumonolide (1) was determined by chiral analysis of the amino acid units and computational methods, followed by NMR chemical shift and ECD spectrum prediction, indicating all‐R configuration for the polyketide portion, as in palmyrolide A and contrary to the all‐S configuration in apratoxins. Functional screening against a panel of 168 GPCR targets revealed tumonolide (1) as a selective antagonist of TACR2 with an IC50 of 7.0 μM, closely correlating with binding affinity. Molecular docking studies established the binding mode and rationalized the selectivity for TACR2 over TACR1 and TACR3. RNA sequencing upon treatment of HCT116 colorectal cancer cells demonstrated activation of the pulmonary fibrosis idiopathic signaling pathway and the insulin secretion signaling pathway at 20 μM, indicating its potential to modulate these pathways. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumours worldwide. Diarylheptanoids, secondary metabolites isolated from Zostera marina, are of interest in natural products research due to their biological activities. Zosterabisphenone B (ZBP B) has recently been shown to inhibit the viability of CRC cells. The aim of this study was to investigate the therapeutic potential of ZBP B for targeting human CRC cells. Cell viability was determined using the MTT assay. Flow cytometry and Western blot analyses were used to assess apoptosis and autophagy. A CRC xenograft model was used to evaluate the in vivo effect of ZBP B. No cytotoxic effect on HCEC cells was observed in the in vitro experiments. ZBP B caused morphological changes in HCT116 colon cancer cells due to an increase in early and late apoptotic cell populations. Mechanistically, ZBP B led to an increase in cleaved caspase‐3, caspase‐8, caspase‐9, PARP and BID proteins and a decrease in Bcl‐2 and c‐Myc proteins. In the xenograft model of CRC, ZBP B led to a reduction in tumour growth. These results indicate that ZBP B exerts a selective cytotoxic effect on CRC cells by affecting apoptotic signalling pathways and reducing tumour growth in mice. Taken together, our results suggest that ZBP B could be a lead compound for the synthesis and development of CRC drugs. [ABSTRACT FROM AUTHOR]

The article discusses the discovery and structure elucidation of a new marine natural product called tumonolide, which has potential as a drug target. Tumonolide is a selective antagonist of the tachykinin receptor 2 (TACR2), a type of G protein-coupled receptor (GPCR) that is a target for many approved drugs. The compound was isolated from a marine cyanobacterium and its structure was determined using spectroscopic and computational methods. The article provides more detailed information on this research. [Extracted from the article]

It has been possible to isolate plakoside A and B from the marine sponge Plakortis simplex. These are unique beta-galactosyl-ceramides. Their galactose residues are alkylated at O-2 by a 3,3-dimethylallyl group. The presence of a prenylated galactose in plakosides is extremely important in relation to their biological activity. All the unsubstituted monoglycosylceramides into which research has been undertaken so far have been found to be immunostimulating, regardless of the nature of the sugar and of the alpha or beta stereochemistry of the glycosidic linkage.

The correlation between stressors and bioindicators can provide evidence of environmental status both as an indication and monitoring tool, and in the identification of the pollutant source. Cyanobacteria possess several hallmark traits of good bioindicators: physiological tolerances or ecological ranges of specific cyanobacterial species can differ depending on taxon-specific cellular requirements. In certain conditions cyanobacteria can form extensive blooms; this phenomenon arising from excessive nutrient input is usually of anthropogenic origin, resulting from a myriad of sources including point sources from municipal and industrial discharges, and non-point sources from agricultural run-off. This work is integrated with the activities carried out within a wider research project aimed at (a) characterizing the role of cyanobacteria as a good bioindicator of coastal water quality, (b) advancing a hierarchical monitoring approach using space-borne remote sensing to in-situ sampling and laboratory microscope analysis of cyanobacteria, (c) reporting on the taxonomic analysis of the cyanobacterial community in the coastal waters of Campania region in southern Italy, and (d) exploring the relationship of cyanobacteria with the terrestrial river basins draining to the coast. In this study, the occurrence of specific cyanobacteria species in extremely polluted environment has been investigated. Specifically, the target point has been selected based on the discharge from the wastewater treatment plant in Cuma, Campania region (Italy). These analyses can support environmental impact studies by governmental officials regarding aquatic pollution problems e.g. determining the effectiveness of wastewater plants in preventing eutrophication impacts within specific coastal areas. [ABSTRACT FROM AUTHOR]

The Caribbean sponge Pseudoceratina crassa yields six crasseride homologues, which are analogues of the glycolipids but are based instead on a five-membered cyclitol. Spectroscopic studies of their tetraacetates reveal a 1'-O-linked propyl 10'-methylhexadecyl ether sidechain. The homologues are differentiated from one another by their acylated branched chain at position-2 of the propyloxy component. Assays show a strong antifeedant action of the glycerides,suggesting their role as feeding deterrents.