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Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. https://www.selleckchem.com/products/GSK690693.html The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone (1) and (1R,7R,8R,11S)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (2), isolated from Eunicea genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC50) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound 9 showed an EC50 = 0.92 ± 0.08 μM and SI = 820 against ZIKV.Three new tyramine-type alkamides (1-3), three new natural products (4-6), five new N-acylated/formylated aporphine alkamides with different ratios of rotational isomers (7-11), and 20 known alkamides (12-31) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of compounds 7, 8, and 10 were determined by single-crystal X-ray diffraction analysis. In the biological activity assay, compounds 3, 5, and 10-23 displayed inhibitory effects against lipopolysaccharide-induced NO release in BV-2 microglial cells, exhibiting IC50 values of 0.93-45 μM.Mass spectrometry imaging is well-suited to characterizing sample surfaces for their chemical content in a spatially resolved manner. However, when the surface contains small objects with significant empty spaces between them, more efficient approaches to sample acquisition are possible. Image-guided mass spectrometry (MS) enables high-throughput analysis of a diverse range of sample types, such as microbial colonies, liquid microdroplets, and others, by recognizing and analyzing selected location targets in an image. Here, we describe an imaging protocol and macroMS, an online software suite that can be used to enhance MS measurements of macroscopic samples that are imaged by a camera or a flatbed scanner. The web-based tool enables users to find and filter targets from the optical images, correct optical distortion issues for improved spatial location of selected targets, input the custom geometry files into an MS device to acquire spectra at the selected locations, and finally, perform limited data analysis and use visualization tools to aid locating samples containing compounds of interest. Using the macroMS suite, an enzyme mutant library of Saccharomyces cerevisiae and nL droplet arrays of Escherichia coli and Pseudomonas fluorescens have been assayed at a rate of ∼2 s/sample.The hypoglycemic activities of the hydrophobic branched-chain amino acid (BCAA) peptides from seabuckthorn seed protein were preliminarily characterized in type 2 diabetic db/db mice. Four novel BCAA peptides (18.27 ± 0.26% (w/w) Leu/Ile-Pro-Glu-Asp-Pro, Asp-Leu/Ile-Val-Gly-Glu, Leu/Ile-Pro, and Leu/Ile-Pro-Leu/Ile) were identified in seabuckthorn seed protein. The protein content in seabuckthorn seed protein hydrolysate, obtained using 80% ethanol, was 78.8 ± 1.4% (w/w). Animal experiments revealed that oral administration of BCAA peptides (all four) significantly reversed the diabetic symptoms. Compared to the db/db group (control), body weight and insulin resistance were ameliorated after treatment with BCAA peptides (0.5, 1.0, 2.0 mg/(g d)). Also, the treatment remarkably reduced the fasting blood glucose (FBG) levels by upregulation of glucose transporter 4 (GULT4). Moreover, BCAA peptides significantly increased the muscle glycogen content (22.6 ± 0.9 nmol/mg) via the downregulation of protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) while increasing the activity of glycogen synthase (GS). BCAA peptides also significantly upregulated the protein levels of phosphatidylinositol 3-kinase (PI3K). We show that BCAA peptides alleviated insulin resistance associated with altered PI3K/Akt protein expression in the skeletal muscle of db/db mice.For the first time, a detailed study on the photophysical properties of variously substituted diazoketones and on their photoreactivity under blue LED irradiation was carried out. Despite very limited absorbance in the visible region, we have demonstrated that, independently from their structure, α-diazoketones all undergo a very efficient Wolff rearrangement. Contrarily to the same UV-mediated reaction, where photons can give rise to side processes, in this case, almost all absorbed photons are selective and effective, and the quantum yield is close to 100%. If the rearrangement is carried out in the presence of isocyanides and carboxylic acids/silanols, the photoreactivity is not affected, and the resulting ketenes can afford α-acyloxy- and α-silyloxyacrylamides through two distinct multicomponent reactions, performed both in batch and under continuous flow, with improved selectivity and broader scope. These photoinduced multicomponent reactions can be coupled with other visible-light-mediated transformations, thus increasing the diversity of the molecules obtainable by this approach.Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.