Peptide cyclisation promoted by supramolecular complex formation

Phenol ester activated dipeptides that are reluctant to ring-closure have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised...

Revealing the Toxicity-Enhancing Essence of Glycyrrhiza on Genkwa Flos Based on Ultra-high-performance Liquid Chromatography Coupled With Quadrupole-Orbitrap High-Resolution Mass Spectrometry and Self-Assembled Supramolecular Technology

Researchers often focus on the mechanisms of synergistic agents, a few explore drug combinations that enhance toxicity, while few have studied the internal mechanism of compatibility enhancement in chemical level. Herein, we present a comprehensive analysis based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and a self-assembled supramolecular strategy, which reveals the toxicity-enhancing essence of glycyrrhizic acid originated in licorice when combined with Genkwa Flos. Through this method, we discovered the toxicity was enhanced through the formation of a supramolecular complex from Genkwa Flos/glycyrrhizic acid. The morphology and size distribution of the self-assembled nanoparticles were characterized by scanning electron microscopy and dynamic light scattering Furthermore, a total of 58 constituents (eight diterpenoids, 35 flavonoids, five phenylpropanoids, four nucleosides, two amino acids, and four other compounds) consisted from the supramolecular complex were identified through accurate-mass measurements in full-scan MS/data-dependent MS/MS mode. Based on the hydrophobic interaction of glycyrrhizic acid with yuanhuacine (one of main ingredients from Genkwa Flos), the supramolecular self-assembly mechanism was revealed with proton nuclear magnetic resonance (1H-NMR) and NOESY 2D NMR. The toxicity of Genkwa Flos and Genkwa Flos/glycyrrhizic acid supramolecular complex were compared through in vitro studies on L-02 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and 4′,6-diamidino-2-phenylindole (DAPI) staining was performed to further confirm the enhancement inhibition of Genkwa Flos/glycyrrhizic acid supramolecular complex than Genkwa Flos. This study provides fundamental scientific evidence of the formation of a self-assembled phytochemical supramolecular when Genkwa Flos and glycyrrhizic acid are combined, enabling to understand their clinical incompatibility and contraindication.

Methodology for application of supramolecular fenbendazole against helminthosis of ruminants

The purpose of the research is developing a methodology for application of the supramolecular complex of fenbendazole (SMCF) against helminthosis in ruminants.The SMCF was obtained by the method of mechanochemical technology with polyvinylpyrrolidone (PVP) in a ratio of 1 : 10 in a balling drum. The drug was produced in plastic cans of 2, 4 and 8 kg and stored in its original packaging in dry, nonresidential area. The SMCF was used against gastrointestinal strongylatosis, dictyocaulosis and monieziosis of sheep and goats at a dose of 20 mg/kg (2 mg/kg for the active substance). The methodology provides a brief chemical characteristic of the SMCF, summarizes its mode of action, and describes toxicological properties, which gives an idea of the drug in general. The procedure is described for preparing the drug for use on animals, both individually and in a group. Reasoned recommendations are given on the timing for animal slaughter, and the use of milk after treating cows.

Methodology for the quantitative determination of fenbendazole and its metabolites in organs and tissues of animals by high performance liquid chromatography with tandem mass spectrometry detection

The purpose of the research is to develop a methodology for the quantitative determination of fenbendazole (FBZ) and its metabolites in organs and tissues of sheep by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS).Materials and methods. The method for determining of FBZ and its metabolites after the administration of the supramolecular complex of fenbendazole was validated in accordance with international guidelines for the following indicators: linearity, recovery, specificity, precision, accuracy, limits of quantitative and qualitative determination.Results and discussion. The method of quantitative analysis of FBZ and its metabolites sulfone and sulfoxide in the body of sheep after the administration of the supramolecular complex has been adapted. The proposed method has a linear relationship (R > 0.99) in the range of 5–1000 ng / g and has shown a good reproducibility and accuracy.

Rational Design of Simple Organocatalysts for the HSiCl3 Enantioselective Reduction of (E)-N-(1-Phenylethylidene)aniline

Prolinamides are well-known organocatalysts for the HSiCl3 reduction of imines; however, custom design of catalysts is based on trial-and-error experiments. In this work, we have used a combination of computational calculations and experimental work, including kinetic analyses, to properly understand this process and to design optimized catalysts for the benchmark (E)-N-(1-phenylethylidene)aniline. The best results have been obtained with the amide derived from 4-methoxyaniline and the N-pivaloyl protected proline, for which the catalyzed process is almost 600 times faster than the uncatalyzed one. Mechanistic studies reveal that the formation of the component supramolecular complex catalyst-HSiCl3-substrate, involving hydrogen bonding breaking and costly conformational changes in the prolinamide, is an important step in the overall process.

Inflammasome Signaling: A Novel Paradigm of Hub Platform in Innate Immunity for Cancer Immunology and Immunotherapy

Inflammasomes are fundamental innate immune mechanisms that promote inflammation and induce an inflammatory form of programmed cell death, pyroptosis. Pyroptotic inflammasome has been reported to be closely associated with tumorigenesis and prognosis of multiple cancers. Emerging studies show that the inflammasome assembly into a higher-order supramolecular complex has been utilized to evaluate the status of the innate immune response. The inflammasomes are now regarded as cellular signaling hubs of the innate immunity that drive the production of inflammatory cytokines and consequent recruitment of immune cells to the tumor sites. Herein, we provided an overview of molecular characteristics and biological properties of canonical and non-canonical inflammasome signaling in cancer immunology and immunotherapy. We also focus on the mechanism of regulating pyroptotic inflammasome in tumor cells, as well as the potential roles of inflammasome-mediated pyroptotic cell death in cancers, to explore the potential diagnostic and therapeutic markers contributing to the prevention and treatment of cancers.