ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Barium titanate‐based nanodielectrics of two chemically recyclable thermosets

In this work was investigated the effect of the addition of barium titanate (BaTiO₃) on electrical properties of two chemically recyclable thermosets, polyhemiaminal (PHA) and polyhexahydro‐s‐triazine (PHT), both fabricated from 4,4′‐oxydianiline (ODA), an ether derivative of aniline and paraformaldehyde. Thermal and mechanical properties as well as chemical recyclability of the two polymers and their nanocomposites/nanodielectrics were also investigated. In addition, a quantitative analysis was conducted of the nanoparticle dispersion in the PHA‐/PHT‐based BaTiO₃‐containing nanocomposites using transmission electron microscopy imaging and the nearest‐neighbor distance index and this index was used to analyze the investigated properties in connection with the proper mechanisms. Regarding the electrical properties for both neat polymers, conductivity values of the order of 10^?8 S m^?1 at 100 Hz were observed and dielectric constant values close to 2.80 for both polymers at 1 kHz. The addition of 0.5 wt% of BaTiO₃ ferroelectric nanoparticles increased by about 44% the dielectric constant (1 kHz) and conductivity (10² Hz) of the PHA‐based nanocomposite. PHA and PHT exhibited glass transition temperature (T_g) values in the range 125–180 °C. An increase of 7 °C in T_g was observed after the incorporation of 0.5 wt% of BaTiO₃ into PHA. Concerning the mechanical properties, values in the range 4.00–4.45 GPa for reduced modulus and 0.30–0.43 GPa for nanohardness for PHA and PHT polymers were observed. Independently of filler content or polymer matrix, both mechanical properties were enhanced after the addition of BaTiO₃. The chemical recycling of PHA/PHT and all nanocomposites in the initial ODA reagent after sulfuric acid treatment was successfully characterized using the NMR and Fourier transform infrared spectroscopic techniques. © 2018 Society of Chemical Industry     

Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.     

Relative expression and regulation by short-term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

Lysophosphatidic acid (lysoPtdOH) levels have previously been reported to decrease in rodents with short-term fasting. We investigated whether a 16 h fast would change expression of autotaxin, the predominant phospholipase D responsible for adipose-derived lysoPtdOH synthesis, or any of the lysophosphatidic acid receptors (1–6) in four white adipose tissue (WAT) depots and interscapular brown adipose tissue (BAT) in male C57Bl/6J mice fed ad libitum, or fasted for 16 h. Aside from small inductions of Lpar1 in epididymal WAT and Lpar2 in epididymal and inguinal WAT, no significant changes were observed in expression of the Lpar family members, or autotaxin in perirenal, retroperitoneal, epididymal, or inguinal WAT or BAT with fasting. Comparison of the relative expression of Lpar1-6 in various depots showed that Lpar6 was the predominant Lpar in both WAT and BAT, and suggests that further work on the adipose-specific role of Lpar6 is warranted.     

Inferring kinetic dissolution of NaCl in aqueous glycol solution using a low-cost apparatus and population balance model

An experimental methodology for inferring brine dissolution rate in monoethylene glycol (MEG) solutions at different temperatures using a webcam combined with a mathematical model is presented. The measurement system is designed to track the RGB (red, green, and blue) colour variations during the dissolution process. A dynamic model augmented with the population balance equation is applied to describe the dissolution process. Moreover, the dissolution rate is consistently related to the temperature and MEG concentration through the driving force based on the Gibbs energy and chemical affinity. The applied low-cost measurement apparatus proved to be a useful resource for tracking the dissolution dynamics in a wide range of undersaturation.