ALBERT

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: The combination of LC-MS/MS based metabolomics approach and anti-MRSA activity-guided fractionation scheme was applied on the Gram-negative bacterium Aequorivita sp. isolated from shallow Antarctic sea sediment using a miniaturized culture chip technique. This methodology afforded the isolation of three new (1–3) and four known (4–7) N-terminal glycine- or serine-bearing iso-fatty acid amides esterified with another iso-fatty acid through their C-3 hydroxy groups. The chemical structures of the new compounds were elucidated using a set of spectroscopic (NMR, [α]D and FT-IR) and spectrometric (HRMS, HRMS/MS) methods. The aminolipids possessing an N-terminal glycine unit (1, 2, 4, 5) showed moderate in vitro antimicrobial activity against MRSA (IC50 values 22–145 µg/mL). This is the first in-depth chemistry and biological activity study performed on the microbial genus Aequorivita.

Description: Correct assignment of the stereogenic centers of highly flexible linear diterpenes (LDs) is challenging. Herein we report the first application of VCD spectroscopy for the absolute configuration determination of LDs of algal origin and provide experimental and computational procedures, such as a fragmentation approach, which will facilitate the use of VCD spectroscopy for configuration assignments of LDs.

Description: Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD) spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

Description: Filamentous fungi are well known for their capability of producing antibiotic natural products. Recent studies have demonstrated the potential of antimicrobials with vast chemodiversity from marine fungi. Development of such natural products into lead compounds requires sustainable supply. Marine biotechnology can significantly contribute to the production of new antibiotics at various levels of the process chain including discovery, production, downstream processing, and lead development. However, the number of biotechnological processes described for large-scale production from marine fungi is far from the sum of the newly-discovered natural antibiotics. Methods and technologies applied in marine fungal biotechnology largely derive from analogous terrestrial processes and rarely reflect the specific demands of the marine fungi. The current developments in metabolic engineering and marine microbiology are not yet transferred into processes, but offer numerous options for improvement of production processes and establishment of new process chains. This review summarises the current state in biotechnological production of marine fungal antibiotics and points out the enormous potential of biotechnology in all stages of the discovery-to-development pipeline. At the same time, the literature survey reveals that more biotechnology transfer and method developments are needed for a sustainable and innovative production of marine fungal antibiotics.

Description: Chemical investigation of the marine sponge Plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides B–K (3–5 and 7–13) and peroxyplakoric esters B3 (6) and C (14). Eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing THF-type ring in the side chain. The library of endoperoxide derivatives was evaluated for in vitro activity against Trypanosoma brucei rhodesiense and Leishmania donovani. Some compounds, such as manadoperoxide B, exhibited ultrapotent trypanocidal activity (IC50 = 3 ng mL−1) without cytotoxicity. Detailed examination of the antitrypanosomal activity data and comparison with those available in the literature for related dioxane derivatives enabled us to draw a series of structure–activity relationships. Interestingly, it appears that minor structural changes, such as a shift of the methyl group around the dioxane ring, can dramatically affect the antitrypanosomal activity. This information can be valuable to guide the design of optimized antitrypanosomal agents based on the dioxane scaffold.

Description: Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6-8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure-activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents.

Description: Herbal medicinal products are commonly used in alternative treatment of menopausal hot flushes. In a recent clinical study, Salvia officinalis tincture was found to reduce hot flush frequency and intensity. The aim of the current study was the investigation of the mechanism(s) responsible for the anti-hot flush activity of S. officinalis and determination of its active principle(s). The 66 % ethanolic tincture, as well as the n-hexane, CHCl3, and aqueous ethanolic subextracts obtained from the tincture were studied in vitro for two of the most relevant activities, estrogenicity and selective serotonin reuptake inhibition. Because of an increased risk of menopausal women to suffer from Alzheimerʼs disease, an in vitro acetylcholinesterase inhibition assay was also employed. No activity was observed in the selective serotonin reuptake inhibition or the acetylcholinesterase inhibition assays at the highest test concentrations. The tincture showed no estrogenic effects whereas the aqueous ethanolic subextract exhibited estrogenicity in the ERLUX assay with an EC50 value of 64 µg/mL. Estrogenic activity-guided fractionation of the aqueous ethanolic subextract by a combination of reverse-phase vacuum liquid chromatography and gel chromatography identified luteolin-7-O-glucuronide (EC50 129 µg/mL) as the active component of the vacuum liquid chromatography fraction 4 (EC50 69 µg/mL). Luteolin-7-O-glucoside was identified as the putative estrogenic principle of the most potent minor fraction (7.6.7.6, EC50 0.7 µg/mL) obtained from the initial vacuum liquid chromatography fraction 7 (EC50 3 µg/mL). This study suggests the involvement of common and ubiquitous estrogenic flavonoids in the anti-hot flush effect of Salvia officinalis, a safe and commonly used herbal medicinal product during the menopause.

Description: The genus Ficus (Moraceae) is well known for antioxidant, anticancer, antidiarrhoeal, antimicrobial, antiplasmodial, antiulcer and gastroprotective activities [1]. In Zambia, the milky latex of some Ficus species is traditionally used against ringworms, while other plant parts are used to treat wounds, chest infections, stomach problems and fevers [2,3]. The folk medicinal knowledge in Zambia is poorly documented and the potential of the medicinal plants has remained unexplored. In this study, we collected the milky latex, as well as the leaves and stem barks of six Ficus species (F. sycomorus, F. sansibarica, F. ovata, F. wakefieldii, F. lutea and F. natalensis) that are native to the Zambezi valley of Zambia. The in vitro antifungal activity of the latex (used directly) and the crude MeOH extracts of the leaves and stem barks were assayed against clinical cultures of two fungi causing ringworm infections (Trichophyton tonsurans and T. interdigitale), as well as a yeast (Candida albicans) and a mould (Aspergillus fumigatus). The agar plate disc and well diffusion techniques were employed by using miconazole and MeOH as positive and negative controls, respectively. Except for the milky latex of F. sansibarica, all other latices and the crude extracts were inactive at 100µg/ml concentration. Previous studies have however, reported significant activity for the crude MeOH extract of F. ovata against a clinical isolate of C. albicans [1], and the activity was attributed to the presence of terpenoids, isoflavonoids and phenolic acids. This is the first antifungal screening study evaluating the antifungal activity of native Zambian Ficus species against various fungi.