Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Interleukin-4 Aggravates LPS-Induced Striatal Neurodegeneration In Vivo via Oxidative Stress and Polarization of Microglia/Macrophages.

The present study investigated the effects of interleukin (IL)-4 on striatal neurons in lipopolysaccharide (LPS)-injected rat striatum in vivo. Either LPS or PBS as a control was unilaterally injected into the striatum, and brain tissues were processed for immunohistochemical and Nissl staining or for hydroethidine histochemistry at the indicated time points after LPS injection. Analysis by NeuN and Nissl immunohistochemical staining showed a significant loss of striatal neurons at 1, 3, and 7 days post LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 days, and was sustained up to 7 days post LPS. Increased levels of IL-4 immunoreactivity were exclusively detected in microglia/macrophages, but not in neurons nor astrocytes. The neutralizing antibody (NA) for IL-4 significantly protects striatal neurons against LPS-induced neurotoxicity in vivo. Accompanying neuroprotection, IL-4NA inhibited activation of microglia/macrophages, production of reactive oxygen species (ROS), ROS-derived oxidative damage and nitrosative stress, and produced polarization of microglia/macrophages shifted from M1 to M2. These results suggest that endogenous IL-4 expressed in LPS-activated microglia/macrophages contributes to striatal neurodegeneration in which oxidative/nitrosative stress and M1/M2 polarization are implicated.

Saccharobisindole, Neoasterric Methyl Ester, and 7-Chloro-4(1H)-quinolone: Three New Compounds Isolated from the Marine Bacterium Saccharomonospora sp.

Analysis of the chemical components from the culture broth of the marine bacterium Saccharomonospora sp. CNQ-490 has yielded three novel compounds: saccharobisindole (1), neoasterric methyl ester (2), and 7-chloro-4(1H)-quinolone (3), in addition to acremonidine E (4), pinselin (5), penicitrinon A (6), and penicitrinon E (7). The chemical structures of the three novel compounds were elucidated by the interpretation of 1D, 2D nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) data. Compound 2 generated weak inhibition activity against Bacillus subtilis KCTC2441 and Staphylococcus aureus KCTC1927 at concentrations of 32 µg/mL and 64 µg/mL, respectively, whereas compounds 1 and 3 did not have any observable effects. In addition, compound 2 displayed weak anti-quorum sensing (QS) effects against S. aureus KCTC1927 and Micrococcus luteus SCO560.

Sarmentosamide, an Anti-Aging Compound from a Marine-Derived Streptomyces sp. APmarine042.

Many bioactive materials have been isolated from marine microorganisms, including alkaloids, peptides, lipids, mycosporine-like amino acids, glycosides, and isoprenoids. Some of these compounds have great potential in the cosmetic industry due to their photo-protective, anti-aging, and anti-oxidant activities. In this study, sarmentosamide (1) was isolated from marine-derived Streptomyces sp. APmarine042, after which its capacity to decrease skin aging was examined in-vitro. Sarmentosamide (1) was found to significantly reduce UVB-induced matrix metalloproteinase-1 (MMP-1) expression in normal human dermal fibroblasts (NHDFs) by inhibiting the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) phosphorylation, which are regulatory pathways upstream of MMP-1 transcription. Additionally, we confirmed that sarmentosamide (1) decreased tumor necrosis factor-alpha (TNF-α), induced MMP-1 secretion in NHDFs, and exhibited free-radical scavenging activity, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Therefore, our study suggests that sarmentosamide (1) could be a promising anti-aging agent that acts via the downregulation of MMP-1 expression.

Marine natural products with monoamine oxidase (MAO) inhibitory activity.

CONTEXT: Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products. OBJECTIVE: To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO. METHODS: Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine. RESULTS: Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources. CONCLUSIONS: This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.

Potent and selective inhibition of human monoamine oxidase-B by 4-dimethylaminochalcone and selected chalcone derivatives.

Six synthetic (1-6) and six natural (7-12) chalcones were tested for human monoamine oxidases (hMAOs) and acetylcholinesterase (AChE) inhibitory activities. Compounds 4-dimethylaminochalcone (2), 4'-chloro-4-dimethylaminochalcone (5), and 2,4'-dichloro-4-dimethylaminochalcone (1) potently inhibited hMAO-B with IC50 values of 0.029, 0.061, and 0.075 µM, respectively. 4-Nitrochalcone (4) and 4-chlorochalcone (3) also potently inhibited hMAO-B with IC50 values of 0.066 and 0.082 µM, respectively (2.3- and 2.6-fold less than compound 2). Compound 2 had a high selectivity index (113.1) for hMAO-B over hMAO-A (IC50 = 3.28 µM). Compounds 1 and 2,2'-dihydroxy-4',6'-dimethoxychalcone (12) potently inhibited hMAO-A with IC50 values of 0.18 and 0.39 µM, respectively. In addition, compounds 4 and 2 also effectively inhibited AChE with IC50 values of 1.25 and 6.07 µM, respectively, and thus, exhibited dual-targeting. Compound 2 reversibly and competitively inhibited hMAO-B with a Ki value of 0.0066 µM. Docking simulations showed binding affinities of compounds 1 to 5 for hMAO-B were higher than those for hMAO-A or AChE and suggested these five chalcones form hydrogen bonds with MAO-B at Cys172 but that they do not form hydrogen bonds with hMAO-A or AChE. These findings suggest compound 2 be considered a promising and dual-targeting lead compound for the treatment of Alzheimer's disease.

Saccharoquinoline, a Cytotoxic Alkaloidal Meroterpenoid from Marine-Derived Bacterium Saccharomonospora sp.

A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spectroscopic data. Saccharoquinoline (1) is composed of a drimane-type sesquiterpene unit in combination with an apparent 6,7,8-trihydroxyquinoline-2-carboxylic acid. This combination of biosynthetic pathways was observed for the first time in natural microbial products. Saccharoquinoline (1) was found to have cytotoxicity against the HCT-116 cancer cell line by inducing G1 arrest, which leads to cell growth inhibition.

Scalalactams A⁻D, Scalarane Sesterterpenes with a γ-Lactam Moiety from a Korean Spongia Sp. Marine Sponge.

Intensive study on the chemical components of a Korean marine sponge, Spongia sp., has led to the isolation of four new scalarane sesterterpenes, scalalactams A⁻D (1⁻4). Their chemical structures were elucidated from the analysis of spectroscopic data including 1D-and 2D-NMR as well as MS data. Scalalactams A⁻D (1⁻4) possess a scalarane carbon skeleton with a rare structural feature of a γ-lactam moiety within the molecules. Scalalactams A and B (1 and 2) have an extended isopropanyl chain at the lactam ring, and scalalactams C and D (3 and 4) possess a phenethyl group at the lactam ring moiety. Scalalactams A⁻D (1⁻4) did not show FXR antagonistic activity nor cytotoxicity up to 100 µM.