Synthesis,Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity

Class I histone deacetylases (HDACs) are key regulators of cell proliferation and they are frequently dysregulated in cancer cells. We report here the synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety. Some of the compounds were additionally substituted with an aromatic capping group. Compounds were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Molecular docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) analysis of this novel series of class-I HDACi. The most potent compounds, including 19f, which blocks HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors 21a and 29b, were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, taking into consideration their low toxicity against human embryonic HEK293 cells. We found that 19f is superior to the clinically tested class-I HDACi Entinostat (MS-275). Thus, 19f is a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.     

Spontaneous Dewetting of Au-Thin Layers on Oxide- and Fluorine-Terminated Single Crystalline Anatase and Efficient Use in Photocatalytic H2 Production

In the present work, the spontaneous dewetting of thin Au layers on single crystalline anatase nanosheets into narrow-disperse Au nanoparticles is investigated. Patterns of the Au particles can be formed on the main facets of anatase that provide a high co-catalytic activity for photocatalytic generation of H₂. Dewetting is distinctly influenced by the respective facets (001) and (101), the deposit thickness, and secondary thermal dewetting, but most strongly by the surface termination of the nanosheets. Fluoride termination not only leads to an enhanced Au-phobic behavior but strongly affects the co-catalytic activity for photocatalytic generation of H₂. While fluoride termination with or without Au decoration is detrimental for hole transfer, the interplay of the Au co-catalyst and surface fluoride yields highly beneficial effect for electron transfer. This results in a three-times higher photocatalytic H₂ production for the F-terminated surface. The findings suggest that dewetting of Au on surface fluorinated TiO₂ is an effective way to modulate surface dewetting and achieve a strongly enhanced photocatalytic activity.     

Template-Directed Polymerization of Binary Acrylate Monomers on Surface-Activated Lignin Nanoparticles in Toughening of Bio-Latex Films

Fabricating bio-latex colloids with core–shell nanostructure is an effective method for obtaining films with enhanced mechanical characteristics. Nano-sized lignin is rising as a class of sustainable nanomaterials that can be incorporated into latex colloids. Fundamental knowledge of the correlation between surface chemistry of lignin nanoparticles (LNPs) and integration efficiency in latex colloids and from it thermally processed latex films are scarce. Here, an approach to integrate self-assembled nanospheres of allylated lignin as the surface-activated cores in a seeded free-radical emulsion copolymerization of butyl acrylate and methyl methacrylate is proposed. The interfacial-modulating function on allylated LNPs regulates the emulsion polymerization and it successfully produces a multi-energy dissipative latex film structure containing a lignin-dominated core (16% dry weight basis). At an optimized allyl-terminated surface functionality of 1.04 mmol g⁻¹, the LNPs-integrated latex film exhibits extremely high toughness value above 57.7 MJ m⁻³. With multiple morphological and microstructural characterizations, the well-ordered packing of latex colloids under the nanoconfinement of LNPs in the latex films is revealed. It is concluded that the surface chemistry metrics of colloidal cores in terms of the abundance of polymerization-modulating anchors and their accessibility have a delicate control over the structural evolution of core–shell latex colloids.     

Augmented grocery shopping: fostering healthier food purchases through AR

Virtual Reality - Food choices are intimately related to individual health. Therefore, the food we buy should be carefully chosen. However, grocery shopping is typically done in noisy environments,...     

Transgression,Innovation, Politics

As partner at Zaha Hadid Architects, Patrik Schumacher has become renowned for his substantial role in taking an experimental practice to a global level. Here he argues for some qualification in the way that transgression might be employed in architecture: Where should transgression stand in relation to a cycle of innovation? Should progress take uneven revolutionary leaps or a smooth accumulative path? By looking outside itself and engaging in political debate, could the architecture of transgression, in fact, be doing no more than burdening the discipline?