Glycopolymeric inhibitors of β‐glucuronidase. III. Configurational effects of hydroxy groups in pendant glyco‐units in polymers upon inhibition of β‐glucuronidase

Two kinds of new glycopolymers, (P(VB‐1‐GlcaH‐co‐AAm), 9 ) and (P(VB‐1‐Glco‐co‐AAm), 10 ), were synthesized through the radical copolymerization of styrene derivatives bearing pendant D ‐glucaric and D ‐gluconic moieties, N‐(p‐vinylbenzyl)‐1‐D ‐glucaramide (VB‐1‐GlcaH, 7 ), and N‐(p‐vinylbenzyl)‐D ‐gluconamide (VB‐1‐Glco, 8 ), with acrylamide (AAm). Glycopolymer 9 bearing the pendant glucaric moiety at the first position inhibited the hydrolysis of a model compound for xenobiotics‐β‐glucuronide conjugates, p‐nitrophenyl β‐D ‐glucuronide, uncompetitively, in contrast to the competitive inhibition in the presence of the corresponding isomeric glycopolymer bearing the pendant D ‐glucaric unit at the sixth position (P(VB‐6‐GlcaH‐co‐AAm), 3 ) reported in our previous article. On the other hand, another copolymer 10 bearing the gluconic moiety was found not to inhibit the hydrolysis as well as the corresponding copolymer bearing pendant gulonic unit (P(VB‐6‐Glco‐co‐AAm), 4 ). These results indicate that the hydrolysis is influenced not only by existence of pendant carboxyl units but also by the direction on the linkage of the glyco‐units to the polymer frame. Therefore the configurational position of hydroxy groups in pendant glyco‐units in macromolecular inhibitors may be essential for the interaction with β‐glucuronidase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4895–4903, 2006     

Physical Treatment Reduces Trypsin Inhibitor Activity and Modifies Chemical Composition of Marama Bean (Tylosema esculentum)

The utility of the marama bean (MB) as an alternative protein source to soybean (SB) can be limited by the high concentration of trypsin inhibitors (TI). The physical treatment of MB has the potential to ameliorate the antinutritional activities of TI and modify other chemical components. Thus, this study investigated the effects of physical treatments on the chemical components and trypsin inhibitor activity (TIA) of raw MB and SB. The bean substrates were subjected to each of the following treatment methods: (1) room temperature (20–22 °C) soaking for 24 h; (2) electric stove cooking at 100 °C for 10, 20, and 30 min; (3) steam autoclaving at a temperature of 110 °C and pressure of 7 pounds per square inch (psi), as well as a temperature of 121 °C and 7 psi for 5, 15, and 30 min; (4) pre-soaked autoclaving at 110 °C (7 psi) and 121 °C (17 psi) for 5, 15, and 30 min. Treated MB and SB had greater (p < 0.05) crude protein content than untreated samples. All the treatments (except 24 h soaking of MB) reduced (p < 0.05) the TIA and ash content. Marama and SB are similar in protein content, but their amino acids profile and TIA are quite different. Soaking for 24 h was less effective in reducing TIA in MB and SB, compared to the thermal methods, and it was detrimental to the ash and amino acids profile of the two beans. Soaking prior to autoclaving yielded beans with the lowest TI concentrations. In conclusion, thermal methods reduced the TI contents and modified the level of proximate components and amino acids profile of the beans.     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Isolation and HPLC Quantitative Determination of 5α-Reductase Inhibitors from Tectona grandis L.f. Leaf Extract

Steroid 5α-reductase plays a crucial role in catalyzing the conversion of testosterone to dihydrotestosterone, which is involved in many androgen-dependent disorders. Leaf-hexane extract from Tectona grandis L.f. has shown promise as a 5α-reductase inhibitor. The objectives of this current study were to isolate and identify 5α-reductase inhibitors from T. grandis leaves and to use them as the bioactive markers for standardization of the extract. Three terpenoid compounds, (+)-eperua-8,13-dien-15-oic acid (1), (+)-eperua-7,13-dien-15-oic acid (2), and lupeol (3), were isolated and evaluated for 5α-reductase inhibitory activity. Compounds 1 and 2 exhibited potent 5α-reductase inhibitory activity, while 3 showed weak inhibitory activity. An HPLC method for the quantitative determination of the two potent inhibitors (1 and 2), applicable for quality control of T. grandis leaf extracts, was also developed. The ethanolic extract showed a significantly higher content of 1 and 2 than found in the hexane extract, suggesting that ethanol is a preferable extraction solvent. This study is the first reported isolation of 5α-reductase inhibitors (1 and 2) from T. grandis leaves. The extraction and quality control methods that are safe and useful for further development of T. grandis leaf extract as an active ingredient for hair loss treatment products are also reported.     

Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.     

Synthesis, Structure and H+/K+-ATPase Inhibitory Activity of Novel Triazolyl Substituted Tetrahydrobenzofuran Derivatives via One-pot Three-component Click Reaction

Eleven triazolyl substituted tetrahydrobenzofuran derivatives were synthesized in high yields as novel H⁺/K⁺‐ATPase inhibitor via one‐pot CuI‐catalyzed three‐component click reaction of azide, secondary amine and 3‐bromopropyne under mild conditions in water. Their structures were characterized by NMR, IR, ESI‐MS, elemental analysis and single‐crystal X‐ray diffraction analysis. Most of the target compounds exhibited better H⁺/K⁺‐ATPase inhibitory activity than commercial omeprazole with IC₅₀ values less than 15 µmol·L^?1. The initial structure‐activity analysis suggested that the triazole substituted by cycloalkyl, aromatic ring or O‐containing side‐chain seemed to be beneficial for enhancing the activity.     

全光亮镀铁工艺的研究

介绍了一种新型的电镀光亮镀的工艺,使用了“抑氢剂”,并用小槽电镀,Hull Cell实验研究了镀液的性能,还运用线性电位扫描法,旋转圆盘电极法测试了镀液的阴极极化性能和整平性能,采用SEM法观察镀层的形貌,实验结果表明：光亮剂的加入可增大铁沉积时的阴极极化,并伴有整作用,而抑氢剂可增大氢在铁上析出的过电位,从而可提高铁沉积的电流效率并降低镀层的应力。     

Improvement of corrosion resistance of AA6061 alloy by tapioca starch in seawater

This study examines the use of tapioca starch for improvement of corrosion resistance of AA6061 alloy in seawater. Gravimetric, potentiodynamic polarization, linear polarization resistance and electrochemical impedance measurements were employed to study the corrosion behavior of AA6061 alloy in seawater. The electrochemical measurements for AA6061 alloy in seawater showed that the presence of tapioca starch significantly decreases the corrosion rates, corrosion current densities (i_corr), and double layer capacitance (C_dl), simultaneously increases the values of polarization resistance (R_p). The inhibition efficiencies increase with increasing of tapioca starch concentration. The Langmuir adsorption isotherm fits well with the experimental data. The nature of adsorption of tapioca starch on the metal surface has also been examined. The analysis of SEM and EDS confirmed the formation of precipitates of tapioca starch on the metal surface, which reduced the overall corrosion reaction.