Due to the potency and selectivity of lyngbyastatin 7 in inhibiting neutrophil elastase, a serine protease involved in numerous diseases, this cyclodepsipeptide was considered as a promising lead and subjected to further developmental studies. Lyngbyastatin 7 displayed a favorable serum and microsomal stability profile. The large-scale synthesis of key building blocks was performed on gram scale with improved yields and simplified purification procedures. To tailor the complex structure, define the minimal pharmacophore, and modulate the physicochemical properties of the lead scaffold, the first pilot library of analogues was designed and synthesized for structure-activity relationship studies. We uncovered the essential role of the side chain, indicating that the minimal structural requirements for elastase inhibition extended beyond the 3-amino-6-hydroxy-2-piperidone (Ahp) and 2-aminobutenoic acid (Abu) moieties conventionally known to convey antiprotease activity and elastase selectivity, respectively. Our studies will facilitate the design and development of this class of elastase inhibitors. Copyright © 2020 American Chemical Society.NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors.  https://www.selleckchem.com/products/CP-673451.html  Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC50 = 7 nM) and analogues were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion in mice. Copyright © 2020 American Chemical Society.Measuring and quantifying the binding of a drug to a protein target inside living cells and thereby correlating biochemical or biophysical activity with target engagement in cells or tissue represents a key step in target validation and drug development. A prototypic target engagement assay should allow for unbiased determination of small molecule-protein interactions in order to confirm cellular mechanism-of-action (MoA) while avoiding major artificial perturbations of cellular homeostasis and integrity. Recently, several new additions to the chemical biology toolbox have expanded our ability to study drug action in intact cells and enabled surveying of intracellular residence time and binding kinetics, which are particularly important for potent receptor ligands and therapeutic moieties with limited therapeutic index. Copyright © 2020 American Chemical Society.Psilocybin, an active component in "magic mushroom", may have the potential to meet the therapeutic needs for a number of indications without the addictiveness and overdose risk of other mind-altering drugs, such as cocaine, heroin, alcohol, methamphetamine, and so forth. The need for new therapies is urgent because addiction, overdose, and suicide deaths have risen throughout the United States and around the world. Anecdotal and contemporary pharmacological reports have provided some indication about the therapeutic use of psilocybin for the treatment of mental health disorders such as major depressive disorder and addiction disorders. In this Viewpoint, I summarize the current state of psilocybin therapeutic research and attempt to provide some insight into future directions on which the scientific community may wish to focus. Copyright © 2020 American Chemical Society.Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants associated with adverse human health outcomes. Environmental justice neighborhoods experience disproportionate environmental health risks. Hurricane Harvey made landfall on August 25, 2017, bringing record rainfall and catastrophic flooding to Houston, Texas, redistributing PAHs in residential soil. We aimed to describe PAH distributions in soil in the Manchester neighborhood of Houston, TX, and identify their potential sources. Soil samples were collected from 24 residential addresses and analyzed for 16 priority PAH concentrations using an accelerated solvent extractor. PAH distribution and source determination were conducted using spatial analysis and isomer ratios. All sample sites detected PAHs in soil, with the total mass ranging from 0.75 to 69.9 ng/g, which were predominantly four-ring structured PAHs. Total PAH concentrations were highest on the northeastern border of the neighborhood, whereas lower overall concentrations of PAHs were found on the southwestern border, at the highest elevation in the watershed. The ratio indeno[1,,3-cd]pyrene (IP) to indeno[1,,3-cd]pyrene plus benzo[ghi]perylene indicated vehicular combustion as the primary source in 19 of 23 samples. After heavy rainfall from Hurricane Harvey in the Manchester neighborhood, PAHs in soil were unevenly distributed throughout the neighborhood, with an accumulation of PAHs in the northeastern edges. Using isomer ratios and spatial analysis, the likely source of PAHs is from use of transportation infrastructure. Copyright 2019, Mary Ann Liebert, Inc., publishers.This study proposes an efficient and fast method of scanning (e.g., television (TV) scan) coupled with digital image processing technology to replace the conventional slow-scan mode as a standard model of acquisition for general-purpose scanning electron microscopy (SEM). SEM images obtained using the proposed method had the same quality in terms of sharpness and noise as slow-scan images, and it was able to suppress the adverse effects of charging in a full-vacuum condition, which is a challenging problem in this area. Two problems needed to be solved in designing the proposed method. One was suitable compensation in image quality using the inverse filter based on characteristics of the frequency of a TV-scan image, and the other to devise an accurate technique of image integration (noise suppression), the position alignment of which is robust against noise. This involved using the image montage technique and estimating the number of images needed for the integration. The final result of our TV-scan mode was compared with the slow-scan image as well as the conventional TV-scan image.