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A total of eight new oxygenated 4-exo-methylene sterols, 1–8, together with one artifact 9 and six known sterols 11–16, were isolated from the marine sponge Theonella swinhoei collected from the Bohol province in Philippines. Structures of sterols 1–8 were determined from 1D and 2D NMR data. Among the sterols, 8α-hydroxytheonellasterol (4) spontaneously underwent an allylic 1,3-hydroxyl shift to produce 15α-hydroxytheonellasterol (9) as an artifact; this was rationalized by quantum mechanical calculations of the transition state. In addition, the 1,2-epoxy alcohol subunit of 8α-hydroxy-14,15-β-epoxytheonellasterol (5) was assigned using the Gauge-Independent Atomic Orbital (GIAO) NMR chemical shift calculations and subsequent DP4+ analysis. Finally, comparison of the 13C chemical shifts of isolated 7α-hydroxytheonellasterol (6) with the reported values revealed significant discrepancies at C-6, C-7, C-8, and C-14, leading to reassignment of the C-7 stereochemistry in the known structure. [ABSTRACT FROM AUTHOR]

Although various anticancer drugs have been developed for the treatment of nonsmall cell lung cancer, chemotherapeutic efficacy is still limited. Natural products such as phytochemicals have been screened as novel alternative materials, but alternative funds such as marine bioresources remain largely untapped. Of these resources, marine sponges have undergone the most scrutiny for their biological activities, including antiinflammatory, antiviral, and anticancer properties. However, the biological mechanisms of the activities of these marine sponges are still unclear. We investigated the anticancer activity of marine sponges collected from Kosrae in Micronesia and examined their mechanisms of action using nonsmall cell lung cancer A549 cells as a model system. Of 20 specimens, the Haliclona sp. (KO1304-328) showed both dose- and time-dependent cytotoxicity. Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability. A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3. The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp. These results indicate that Haliclona sp. induces apoptosis via the JNK-p53 pathway and caspase-8, suggesting that this marine sponge is a good resource for the development of drugs for treatment of nonsmall cell lung cancer. [ABSTRACT FROM AUTHOR]

AmpC BER is an extended-spectrum (ES) class C β-lactamase with a two-amino-acid insertion in the H 10 helix region located at the boundary of the active site compared with its narrow spectrum progenitor. The crystal structure of the wild-type AmpC BER revealed that the insertion widens the active site by restructuring the flexible H 10 helix region, which is the structural basis for its ES activity. Besides, two sulfates originated from the crystallization solution were observed in the active site. The presence of sulfate-binding subsites, together with the recognition of ring-structured chemical scaffolds by AmpC BER, led us to perform in silico molecular docking experiments with halisulfates, natural products isolated from marine sponge. Inspired by the snug fit of halisulfates within the active site, we demonstrated that halisulfate 3 and 5 significantly inhibit ES class C β-lactamases. Especially, halisulfate 5 is comparable to avibactam in terms of inhibition efficiency; it inhibits the nitrocefin-hydrolyzing activity of AmpC BER with a K i value of 5.87 μM in a competitive manner. Furthermore, halisulfate 5 displayed moderate and weak inhibition activities against class A and class B/D enzymes, respectively. The treatment of β-lactamase inhibitors (BLIs) in combination with β-lactam antibiotics is a working strategy to cope with infections by pathogens producing ES β-lactamases. Considering the emergence and dissemination of enzymes insensitive to clinically-used BLIs, the broad inhibition spectrum and structural difference of halisulfates would be used to develop novel BLIs that can escape the bacterial resistance mechanism mediated by β-lactamases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Three new phenazine derivatives ( 1 - 3 ), along with known compounds ( 4 - 7 ) of saphenic acid derivatives, were isolated from a deep-sea sediment-derived yeast-like fungus Cystobasidium larynigs collected from the Indian Ocean. The structures of the new compounds ( 1 - 3 ) were determined by analysis of spectroscopic data, semi-synthesis and comparison of optical rotation values. All the isolated compounds ( 1 - 7 ), except for 2 , showed nitric oxide (NO) production inhibitory effect against lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells without cytotoxicity at concentrations up to 30 μg/mL. This is the first report on the yeast-like fungus Cystobasidium laryngis producing phenazines and anti-inflammatory activity of 1 - 7 including saphenic acid ( 4 ).

We describe a synthetic approach for a set of fluorescent thieno[3,2- b]pyridine-5(4 H)-one derivatives and their photophysical properties. These fluorophores are prepared by a series of reactions employing the Suzuki-Miyaura cross-coupling reaction and a regioselective aza-[3 + 3] cycloaddition of 3-aminothiophenes with α,β-unsaturated carboxylic acids. Our findings revealed that the photophysical properties are chemically tunable by an appropriate choice of functional group on the thieno[3,2- b]pyridine-5(4 H)-one scaffold.

In the course of our ongoing research for antimicrobial agents, we isolated five new compounds, three 24-membered macrolactones, macrolactins X-Z (1-3) and two hydroxy unsaturated fatty acids, linieodolides A (5) and B (6), together with a known metabolite, macrolactinic acid (4), from the culture broth of a marine Bacillus sp. The structures of these metabolites were determined on the basis of their spectroscopic data interpretation. Their absolute configurations were addressed by modified Mosher's method and literature data review. Compounds 1-6 showed moderate to potent inhibitory activities (8∼128 μg ml(-1)) against selected pathogenic microorganisms.

1-Acetyl-beta-carboline was isolated as an anti-MRSA agent from the fermentation broth of a marine actinomycete isolated from marine sediment. The producing strain was identified to be Streptomyces sp. by phylogenetic analysis of the 16S rRNA gene sequence. The anti-MRSA agent was isolated by bioactivity-guided fractionation of the culture extract by solvent partitioning, ODS open flash chromatography, and purification with a reversed-phase HPLC. Its structure was elucidated by extensive 2D NMR and mass spectral analyses. Combination of 1-acetyl-beta- carboline with ampicillin exhibited synergistic antibacterial activity against MRSA.

Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-alpha-induced NF-kappaB activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of NF-kappaB activation and can be a basis for the development of novel anti-angiogenic agents.