Synthesis and characterisation of novel glycoclusters based on cell penetrating heptakis(6-aminoethylamino-6-deoxy)-??-cyclodextrin

The modification of a polyamino ??CD, heptakis(6-aminoethylamino-6-deoxy)-??CD (bpen) with several monosaccharides (Man, GlcNAc, Gal, Glc), specific for bacterial lectin targeting is described. The first synthetic approach, based on disuccinimidyl carbonate-substituted monosaccharides had moderate success, whereas the second approach, based on thiopropanoic acid-linked monosaccharides, was more efficient. Each method gave the best result with a different monosaccharide. Given that bpen is known to penetrate cells, the new products are expected to possess both lectin recognition ability and membrane crossing properties.     

Tamoxifen subcellular localization; observation of cell-specific cytotoxicity enhancement by inhibition of mitochondrial ETC complexes I and III

Recently, a nongenomic cytotoxic component of the chemotherapeutic agent tamoxifen (TAM) has been identified that predominantly triggers mitochondrial events. The present study delineates the intracellular fate of TAM and studies its interaction with a spectrum of cell homeostasis modulators primarily relevant to mitochondria. The subcellular localization of TAM was assessed by confocal fluorescence microscopy. The effect of the modulators on TAM cytotoxicity was assessed by standard MTT assays. Our findings show that in estrogen receptor positive MCF7 breast adenocarcinoma cells and DU145 human prostate cancer cells, TAM largely accumulates in the mitochondria and endoplasmic reticulum, but not lysosomes. Our results further demonstrate that in MCF7, but not in DU145 cells, mitochondrial electron transport chain complex I and III inhibitors exacerbate TAM toxicity with an order of potency of myxothiazol ≥ stigmatellin > rotenone > antimycin A, suggesting a cell-specific cytotoxic interplay between mitochondrial complex I and III function and TAM action.     

ILs and MMPs Levels in Inflamed Human Dental Pulp: A Systematic Review

A wide range of mediators are released from the pulp tissue because of bacterial invasion which causes inflammation. Interleukins (ILs) and matrix metalloproteinases (MMPs) have a leading role in initiating and spreading of inflammation because of their synergic action. Biomarkers such as ILs and MMPs can be identified via several methods, establishing the inflammatory response of the dental pulp. The aim of this systematic review is to evaluate the levels of ILs and/or MMPs in human dental pulp. PubMed, OVID, Cochrane, Scopus, Web of Science and Wiley online library databases were searched for original clinical studies. After applying inclusion and exclusion criteria, a quality assessment of studies was performed based on a modified Newcastle-Ottawa scale. In the review were included articles that evaluated the presence of ILs and/or MMPs in pulp tissue using enzyme-linked immunosorbent assay (ELISA) or western blot or multiplex assay. Six articles were included in the present synthesis. Although various diagnostic methods were used, statistically significant higher levels of ILs and/or MMPs were mostly found in the experimental groups compared to healthy pulp samples. The biomarkers studied can be a promising tool to evaluate pulp tissue health or even in pulpitis treatment.     

Capturing and prioritizing students’ requirements for course design by embedding Fuzzy-AHP and linear programming in QFD

Customer requirements play a vital and important role in the design of products and services. Quality Function Deployment (QFD) is a popular, widely used method that helps translate customer requirements into design specifications. Thus, the foundation for a successful QFD implementation lies in the accurate capturing and prioritization of these requirements. This paper proposes and tests the use of an alternative framework for prioritizing students’ requirements within QFD. More specifically, Fuzzy Analytic Hierarchy Process (Fuzzy-AHP) and the linear programming method (LP-GW-AHP) based on Data Envelopment Analysis (DEA) are embedded into QFD (QFD-LP-GW-Fuzzy AHP) in order to account for inherent subjectivity of human judgements. The effectiveness of the proposed framework is assessed in capturing and prioritizing students’ requirements regarding courses’ learning outcomes within the process of an academic course design. Sensitivity analysis evaluates the robustness of the prioritization solution and implications for course design specifications are discussed.     

A study of various self deposition solutions for 210Po analysis in tap water

The purpose of the present study was to examine the use of various inorganic acids as self deposition solutions and their macroscopic effects on nickel plates which could potentially deteriorate polonium analysis in tap water. 0.5 M, 2 M and 0.1 M hydrochloric acid solutions in addition to 0.1 M and 0.5 M solutions of nitric, hydrofluoric, hydrobromic, hydriodic, sulfuric, phosphoric, sulfamic and perchloric acid were studied and compared. Polonium was plated via self deposition while the chemical recoveries were determined by alpha spectrometry.

     

9-Substituted acridines. Demethoxylation of 9-methoxyacridine and dechlorination of 9-chloroacridine in hydroxylic solvents

In methanol-water mixtures containing sodium or potassium hydroxide (up to 2.00M) the demethoxylation of 9-methoxyacridine to 9-acridone is of first order in both the free form of 9-methoxyacridine and the hydroxyl ion. The rate of the reaction is increased with an increase in the concentration of water. Sodium perchlorate has a small retarding effect on the reaction. In methanol-water mixtures containing perchloric or hydrochloric acid (up to 3.45M) the demethoxylation is of first order with respect to the protonated form of 9-methoxyacridine. The rate of the reaction decreases with an increase in the concentration of the acid or of sodium perchlorate, but when the concentration of water is increased (≈?1.7 to 50M) and that of the acid is not changed, it reaches a maximum value in mixtures containing 8 to 10M-water. The dechlorination of 9-chloroacridine to 9-methoxyacridine in methanol containing sodium hydroxide or methoxide (up to 0.31 M) is of first order in both the 9-chloroacridine and the hydroxyl or methoxyl ions.     

Comparative Study of a Series of 99mTc(CO)3 Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to ^99mTc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with ^99mTc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10–500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[^99mTc(CO)₃]⁺ synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, ^99mTc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.     

Unexpected one-pot synthesis of new polycyclic coumarin[4,3-c]pyridine derivatives via a tandem hetero-Diels-Alder and 1,3-dipolar cycloaddition reaction

O-Methyl-4-coumarincarbaldehyde oxime reacted as an azadiene with electron-deficient and electron-rich dienophiles to give, via one-step hetero-Diels-Alder cycloaddition reactions, the corresponding 5H-coumarin[4,3-c]pyridin-5-ones. When excess of the dienophile was used, fused azatetracyclo derivatives were also formed via a tandem Diels-Alder and 1,3-dipolar cycloaddition reaction of the dienophile to an azomethine ylide formed by the intermediate 2,3-dihydro-5H-coumarin[4,3-c]pyridine-5-one. The regio- and stereoselectivities of the new compounds correspond well with spectroscopic (2D NMR) and theoretical data. A possible mechanistic scheme is provided.     

Natural and Nature-Derived Products Targeting Human Coronaviruses

The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.