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The complex nature of multifactorial diseases, such as Morbus Alzheimer, has produced a strong need to design multitarget-directed ligands to address the involved complementary pathways. We performed a purposive structural modification of a tetratarget small-molecule, that is contilisant, and generated a combinatorial library of 28 substituted chromen-4-ones. The compounds comprise a basic moiety which is linker-connected to the 6-position of the heterocyclic chromenone core. The syntheses were accomplished by Mitsunobu- or Williamson-type ether formations. The resulting library members were evaluated at a panel of seven human enzymes, all of which being involved in the pathophysiology of neurodegeneration. A concomitant inhibition of human acetylcholinesterase and human monoamine oxidase B, with IC50 values of 5.58 and 7.20 μM, respectively, was achieved with the dual-target 6-(4-(piperidin-1-yl)butoxy)-4H-chromen-4-one (7).
Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.
Scratch assays enable the study of the migration process of an injured adherent cell layer in vitro. An apparatus for the reproducible performance of scratch assays and cell harvesting has been developed that meets the requirements for reproducibility in tests as well as easy handling. The entirely autoclavable setup is divided into a sample translation and a scratching system. The translational system is compatible with standard culture dishes and can be modified to adapt to different cell culture systems, while the scratching system can be adjusted according to angle, normal force, shape, and material to adapt to specific questions and demanding substrates. As a result, a fully functional prototype can be presented. This system enables the creation of reproducible and clear scratch edges with a low scratch border roughness within a monolayer of cells. Moreover, the apparatus allows the collection of the migrated cells after scratching for further molecular biological investigations without the need for a second processing step. For comparison, the mechanical properties of manually performed scratch assays are evaluated.
Due to global ecological and economic challenges that have been correlated to the transition from fossil-based to renewable resources, fundamental studies are being performed worldwide to replace fossil fuel raw materials in plastic production. One aspect of current research is the development of lignin-derived polyols to substitute expensive fossil-based polyol components for polyurethane and polyester production. This article describes the synthesis of bioactive lignin-based polyurethane coatings using unmodified and demethylated Kraft lignins. Demethylation was performed to enhance the reaction selectivity toward polyurethane formation. The antimicrobial activity was tested according to a slightly modified standard test (JIS Z 2801:2010). Besides effects caused by the lignins themselves, triphenylmethane derivatives (brilliant green and crystal violet) were used as additional antimicrobial substances. Results showed increased antimicrobial capacity against Staphylococcus aureus. Furthermore, the coating color could be varied from dark brown to green and blue, respectively.