ALBERT

Description: Highlights: • Improved Claisen-Schmidt condensation using lithium hydroxide monohydrate in 1,4-dioxane. • Pyridylchalcones show good activity and selectivity against Trypanosoma brucei. • Pyridylchalcones show little activity against Leishmania donovani. • Promising leads in the development of novel compounds for the treatment of sleeping sickness. A library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC50 value of 0.29 μM. Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT).

Description: Linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. This study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the Irish brown alga Bifurcariabifurcata. The gross structure of this new natural product was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS). Its absolute configuration was identified by experimental and computational vibrational circular dichroism (VCD) spectroscopy, combined with the calculation of 13C-NMR chemical shielding constants. Bifurcatriol (1) was tested for in vitro antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani) and cytotoxicity against mammalian primary cells. The highest activity was exerted against the malaria parasite P. falciparum (IC50 value 0.65 μg/mL) with low cytotoxicity (IC50 value 56.6 μg/mL). To our knowledge, this is the first successful application of VCD and DP4 probability analysis of the calculated 13C-NMR chemical shifts for the simultaneous assignment of the absolute configuration of multiple stereogenic centers in a long-chain acyclic natural product.

Description: Imaging mass spectrometry (IMS) has recently established itself in the field of "spatial metabolomics." Merging the sensitivity and fast screening of high-throughput mass spectrometry with spatial and temporal chemical information, IMS visualizes the production, location, and distribution of metabolites in intact biological models. Since metabolite profiling and morphological features are combined in single images, IMS offers an unmatched chemical detail on complex biological and microbiological systems. Thus, IMS-type "spatial metabolomics" emerges as a powerful and complementary approach to genomics, transcriptomics, and classical metabolomics studies. In this review, we summarize the current state-of-the-art IMS methods with a strong focus on desorption electrospray ionization (DESI)-IMS. DESI-IMS utilizes the original principle of electrospray ionization, but in this case solvent droplets are rastered and desorbed directly on the sample surface. The rapid and minimally destructive DESI-IMS chemical screening is achieved at ambient conditions and enables the accurate view of molecules in tissues at the µm-scale resolution. DESI-IMS analysis does not require complex sample preparation and allows repeated measurements on samples from different biological sources, including microorganisms, plants, and animals. Thanks to its easy workflow and versatility, DESI-IMS has successfully been applied to many different research fields, such as clinical analysis, cancer research, environmental sciences, microbiology, chemical ecology, and drug discovery. Herein we discuss the present applications of DESI-IMS in natural product research.

Description: In vivo confocal Raman microscopy (CRM), polarized light microscopy and Fourier transform infrared spectroscopy (FTIR) were used to determine if a significant amount of amorphous calcium carbonate (ACC) exists within larval shells of Baltic mytilid mussels (Mytilus edulis-like) and whether the amount of ACC varies during larval development. No evidence for ACC was found from the onset of shell deposition at 21 h post-fertilization (hpf) until 48 hpf. Larval Mytilus shells were crystalline from 21 hpf onwards and exhibited CRM and FTIR peaks characteristic of aragonite. Prior to shell deposition at 21 hpf, no evidence for carbonates was observed through in vivo CRM.We further analysed the composition of larval shells in three other bivalve species, Mercenaria mercenaria, Crassostrea gigas and Crassostrea virginica and observed no evidence for ACC, which is in contrast to previous work on the same species. Our findings indicate that larval bivalve shells are composed of crystalline aragonite and we demonstrate that conflicting results are related to sub-optimal measurements and misinterpretation of CRM spectra. Our results demonstrate that the common perception that ACC generally occurs as a stable and abundant precursor during larval bivalve calcification needs to be critically reviewed.

Description: Due to longer evolutionary history, highly competitive environments with complex ecological interactions and unsurpassable biological diversity, marine organisms have proven to be outstanding sources for potent and chemically diverse molecules for discovery of drugs and functional ingredients. However, these efforts are severely hampered due to low supply, legal and physical access issues and chemical complexity of marine natural products for rapid dereplication and/or full structure elucidation. Another major problem for the exploitation of marine natural products (MNPs) is the ambiguity of their metabolic (natural) source. Although most MNPs are reported from marine invertebrates, 16 of the 20 MNPs that are or were recently undergoing clinical trials against cancer have their origin in (symbiotic) microorganisms [1]. However, less than 1% of the estimated microbial diversity is cultivable, and many biosynthetic gene clusters within this 1% largely remain silent or underexpressed in artificial laboratory conditions [2]. As a result, vast majority of marine secondary metabolites escape detection/annotation and their potential for discovery remain in total darkness. Hence, efficient marine biodiscovery requires innovative approaches and a great analytical chemistry infrastructure. This presentation will describe our efforts for identification of metabolic and microbiome profile of deep-sea organisms and some aquacultured shellfish species. Our on-going studies to promote chemical diversity of marine microbes by employing OSMAC and co-culturing techniques and visualization/localization of MNPs by chemical imaging will also be highlighted.

Description: The marine fungal natural products (MaFNaP) Consortium, a scientific network founded in 2014, aims to fuel systematic research on marine fungi and their secondary metabolites. The 2nd international conference of marine fungal natural products (MaFNaP_2017) that was held in Kiel (Germany) and hosted by GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech) in June 2017 brought together scientists working all relevant aspects of marine fungi. This conference report highlights the topics discussed in the conference and suggestions for future work on marine fungal compounds. One of the major aims is to attract scientists working on terrestrial fungi in tackling the common bottlenecks and to move marine fungal biodiscovery and biotechnology research forward.

Description: The majority of marine natural products (MNPs) originate from tropical and temperate shallow water invertebrates, such as sponges [1]. Recent studies indicate the presence of great genetic diversity in deep-waters that may be linked to unprecedented chemistry due to evolution/adaptation to extremely harsh environmental conditions. However, only less than 2% of MNPs derive from the deep-sea organisms [2]. Antarctic ecosystems are rich in biodiversity [3] and exposed to unique environmental characteristics resulting in communities structured both by biotic interactions (e.g. predation, competition) and abiotic factors (e.g. seasonality, ice-scouring) [4], suggesting a high chemical diversity. In this work, we investigated 39 deep-water sponges collected from the Antarctic Weddell Sea and adjacent areas (depths -100 – 600 m). The freeze-dried sponge samples were extracted with water, followed by MeOH and CH2Cl2 separately. The combined organic extracts were tested for activity against cancer cells [HepG2 (liver) and HT29 (bowel) cancer cell lines], bacteria [ESKAPE panel: Enterococcus faecalis, Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli) and fungi (yeasts Candida albicans, Cryptococcus neoformans). Several Latrunculia sponge extracts displayed high anticancer activity against both cell lines (IC50 values 0.50 – 3.16 µg/ml). The organic extract of the glass sponge Rossella cf. antarctica showed moderate antibiotic activity towards MRSA and E. faecalis with IC50 values of 96 and 213 µg/ml, respectively. All extracts have undergone chemical profiling/dereplication studies by HPLC-DAD-MS and 1H NMR spectroscopy. The results of chemical and biological screening will assist in selection and activity-guided isolation of Antarctic deep-water sponge metabolites.