The discovery of novel natural products (NPs) that will serve as lead structures has to be an ongoing effort to fill the respective development pipelines. However, identification of NPs, which possess a potential for application in e.g., the pharma or agro sector, must be as cost effective and fast as possible. Furthermore, the amount of sample available for initial testing is usually very limited, not least because of the fact that the impact on the environment, i.e., the sampled biosystem, should be kept minimal. Here, our pipeline SeaPEPR is described, in which a primary bioactivity screening of crude extracts is combined with the analysis of their metabolic fingerprint. This enabled prioritization of samples for subsequent microfractionation and dereplication of the active compounds early in the workflow. As a case study, 76 marine sponge-derived extracts were screened against a microbial screening panel. Thereunder, human pathogenic bacteria (Escherichia coli ATCC35218 and Staphylococcus aureus ATCC33592) and yeast (Candida albicans FH2173), as well as the phytopathogenic fungus Septoria tritici MUCL45407. Overall, nine extracts revealed activity against at least one test organism. Metabolic fingerprinting enabled assigning four active extracts into one metabolic group; therefore, one representative was selected for subsequent microfractionation. Dereplication of the active fractions showed a new dibrominated aplysinopsin and a hypothetical chromazonarol stereoisomer derivative. Furthermore, inhibitory activity against the common plant pest Septoria tritici was discovered for NPs of marine origin.

Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone ≈ dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and γH2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via BAX, BIM, and caspase-9 as the main cell death pathway. Interestingly, the compounds were equally effective in p53-wild-type and p53-mutant CRC cells. Finally, the cytotoxic activity of the merosesquiterpenes was corroborated in intestinal tumor organoids, emphasizing their potential for CRC chemotherapy.

To date, exploration of Gracilaria and Gelidiella’s bioactive compounds has been conducted using conventional methods that require a long time, high costs, and significant effort. Currently, metabolomic profiling and molecular networking have emerged as methods of exploring bioactive compounds. This study aimed to perform bioactive compound profiling through a metabolomic LC-HRMS-based and molecular networking approach in Gelidiella acerosa, Gracilaria arcuata, and Gracilaria verrucosa. All chromatograms and MS/MS spectra obtained for three crude extracts were digitally converted into an mzXML file using MSConvert, submitted to the Global Natural Product Social (GNPS), and visualized in Cytoscape 3.9.1. In total, nine dereplicated compounds were identified: 11-Deoxyprostaglandin (m/z 324.214), Diacylglyceryl trimethylhomoserines (DGTS) (m/z 684.575), Glycochenodeoxy acid (m/z 448.369), Lysophosphatidylcholine (m/z 522.350), Diacylglyceryl trimethylhomoserines (DGTS) (m/z 656.557), Pheophorbide A (m/z 593.266), Pyropheophorbide A (m/z 593.266), (2R,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-chromen-4-one (m/z 303.15), and Polyporic acid (m/z 293.156). These compounds are typically classified as fatty acids, lipids, terpenoids, alkaloids, shikimates, and phenylpropanoids. The molecular networking and metabolite clustering showed an interesting pattern where some compounds were produced only by one species, some by two species, and some by all three. These compounds may have pharmaceutical potential based on their chemical properties and reported activities.

The increasing anthropogenic activities in Menjangan Kecil Waters can reduce the health condition of coral reefs in these waters. Therefore, it is necessary to investigate the level of bleaching attack that occurs in these waters. The purpose of this study was to determine the health condition of coral reefs in Menjangan Kecil Waters by observing the level of bleaching attack based on coral colour which is related to the density of zooxanthellae in coral living tissue. The CoralWatch method was applied to estimate the level of bleaching attack based on the level of coral colour in the coral health chart table. The results of this study revealed that the condition of coral reefs at 4 stations was dominated by colour levels 3-4, meaning that the condition of coral reefs began to bleach. The increasing of anthropogenic activities causes excessive interaction with coral reefs and human, thus accelerating the potential for bleaching. Optimization of ecotourism in Menjangan Kecil Waters, Karimunjawa needs to be done by conducting further studies on coral reef health.

Gracilaria edulis, a red seaweed that is widely known as an agar-producing seaweed, has a unique biosynthetic pathway for producing bioactive compounds. However, most of the bioactive compounds of this species have not explored yet. The environmental conditions as well as the extraction method might influence the bioactive compound production. Hence, this study aimed to explore untargeted liquid chromatography–high resolution mass spectrometry (LCHRMS)-based metabolomics profiling of G. edulis (Gracilariales, Rhodophyta) from three different beaches along the southern part of the Special Region of Yogyakarta (Java Island, Indonesia), which has different environmental characteristics. We also observed the effect of extraction solvent on metabolomic profiling of G. edulis extract using three different solvents with the different polarity. Metabolomic profiling was performed using an LC-HRMS instrument and analyzed using the Global Natural Product Social Molecular Networking (GNPS) database. The results revealed differences in the metabolomic profiles of G. edulis’s extracts based on coastal location and solvent. G. edulis from Kukup Beach exhibited the highest metabolomic diversity (277 nodes), followed by G. edulis from Sepanjang Beach (268) and G. edulis from Krakal Beach (204). Among the solvents, n-hexane was the most effective, extracting 311 nodes, followed by methanol (293) and ethyl acetate (197). Nine tentatively dereplicated compounds were found, i.e., pumilacidine C, pumilacidine E, lichenysin, cholesterol, AC1L1X1Z, sarmentoside B, 7-dehydrocholesterol, pheophytin A and porphyra-334. Some dereplicated compounds were found in a specific area. For example, lichenysin and pumilacidin compounds were produced by G. edulis from Sepanjang Beach, while cholesterol and AC1L1X1Z were found in from G. edulis extract, which were collected from Sepanjang and Kukup Beaches, and 7-dehydrocholesterol and sarmentoside B compounds from all beach locations, while pheophytin A and porphyra-334 from Krakal Beach. Further research is needed to obtain pure compounds that have the potential to be antibacterial, as well as antioxidant, anti-inflammatory, and photoprotective compounds.

Background/Objectives: The rise in antimicrobial resistance is one of the major challenges to global health systems, which necessitates the development of new antibacterial compounds. The bioactive compounds of brown seaweed Sargassum duplicatum have demonstrated potential antibacterial activity. This study applied metabolomic profiling and molecular networking in combination with antibacterial screening assays to assess the antimicrobial properties of S. duplicatum extracts against multidrug-resistant bacteria. Methods: Two extraction methods, i.e., maceration and microwave extraction, were used. Therewith, untargeted metabolomic profiling was performed using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Molecular networks (MNs) were established and compound dereplication was conducted using the spectral database of the Global Natural Products Social Molecular Networking platform (GNPS). Additionally, antimicrobial assays were conducted against Gram-positive and Gram-negative bacterial strains, including multidrug-resistant bacteria, i.e., methicillin-resistant Staphyloccocus aureus ATCC 33592 (MRSA) and β-lactamase, producing Escherichia coli ATCC 35218 (TEM-1 positive strain). Result: Dereplication resulted in the prediction of six compounds with reported antimicrobial properties, i.e., 13-docosenamide, 9-octadecenamide, pheophorbide A, ouabain, sarmentoside B and AC1L1X1Z. Antibacterial screening of the extracts revealed that the ethyl acetate maceration extracts exhibited the strongest inhibitory activity, with inhibition values between 85 and 98% against S. aureus ATCC 33592. Conclusions: This metabolomics study requires further research to isolate, purify, confirm, and validate the dereplicated compounds that may have potential antibacterial activity.