Cyclopenta[ b]indole Derivative Inhibits Aurora B in Primary Cells

The Aurora family of kinases is closely involved in regulating cell division. Inhibition of Aurora A and B with small molecules is currently being investigated in clinical trials for the treatment of different cancers. It has also been evaluated as a treatment option against different autoimmune diseases in preclinical studies. Here, we present a cyclopenta[b]indole derivative capable of inhibiting Aurora B selectively in kinase assays. To evaluate the Aurora B inhibition capacity of the compound, we used a kinase IC50 assay as well as a suppression assay of proliferating primary cells. In addition, we examined if the cells had gained a phenotype characteristic for Aurora B inhibition after treatment with the compound. We found that the compound selectively inhibited Aurora B (IC50 = 1.4 μM) over Aurora A (IC50 > 30 μM). Moreover, the compound inhibited proliferating PBMCs with an IC50 = 4.2 μM, and the cells displayed reduced phosphorylation of histone H3 as well as tetraploidy, consistent with Aurora B inhibition

Exceptionally rapid oxime and hydrazone formation promoted by catalytic amine buffers with low toxicity

Hydrazone and oxime bond formation between α-nucleophiles (e.g. hydrazines, alkoxy-amines) and carbonyl compounds (aldehydes and ketones) is convenient and is widely applied in multiple fields of research. While the reactants are simple, a substantial drawback is the relatively slow reaction at neutral pH. Here we describe a novel molecular strategy for accelerating these reactions, using bifunctional buffer compounds that not only control pH but also catalyze the reaction. The buffers can be employed at pH 5-9 (5-50 mM) and accelerate reactions by several orders of magnitude, yielding second-order rate constants of >10 M-1s-1. Effective bifunctional amines include 2-(aminomethyl)imidazoles and N,N-dimethylethylenediamine. Unlike previous diaminobenzene catalysts, the new buffer amines are found to have low toxicity to human cells, and can be used to promote reactions in cellular applications

Intertwining caring science, caring practice and caring education from a lifeworld perspective—two contextual examples

This article describes how caring science can be a helpful foundation for caring practice and what kind of learning support that can enable the transformation of caring science into practice. The lifeworld approach is fundamental for both caring and learning. This will be illustrated in two examples from research that show the potential for promoting health and well-being as well as the learning process. One example is from a caring context and the other is from a learning context. In this article, learning and caring are understood as parallel processes. We emphasize that learning cannot be separated from life and thus caring and education is intertwined with caring science and life. The examples illustrate how an understanding of the intertwining can be fruitful in different contexts. The challenge is to implant a lifeworld-based approach on caring and learning that can lead to strategies that in a more profound way have the potential to strengthen the person's health and learning processes

Oxidative Coupling as a Biomimetic Approach to the Synthesis of Scytonemin

The first total synthesis of the dimeric alkaloid pigment scytonemin is described. The key transformations In Its synthesis from 3-indole acetic acid are a Heck carbocyclization and a Suzuki-Miyaura cross-coupling, orchestrated In a stereospecific tandem fashion, followed by a biosynthetically inspired oxidative dimerization. The tandem sequence generates a tetracyclic (E)-3-(arylidene)-3,4-dihydrocyclopenta[b]indol-2(1H)-one that is subsequently dimerized into the unique homodimeric core structure of scytonemin

Total Synthesis of Nostodione A, a Cyanobacterial Metabolite

The first total synthesis of the mitotic spindle poison nostodione A is described. The inherent oxidative sensitivity of indoles is utilized for a late introduction of a second carbonyl to the cyclopent[b]indole-2-one system. The tricyclic system is prepared from indole-3-acetic acid and O-silylated 4-ethynylphenol, using a stereoselective intramolecular reductive Heck cyclization as the key transformation

Catalytic Iodination of the Aliphatic C-F Bond by YbI3(THF)(3): Mechanistic Insight and Synthetic Utility

A facile iodination protocol, of unactivated alkyl fluorides: using catalytic amounts of YbI3(THF)(3) in the presence of iodotrimethylsilane as a stoichiometric fluoride trapping agent is presented. H-1 NMR spectroscopy demonstrates a two-step :catalytic cycle where TMSI regenerates active YbI3(THF)(3). Finally, the catalytic reaction is extended a one-pot procdure to demonstrate a potential application of the method Overall, the findings present a distinct strategy for C-F bond transformations in the presence of catalytic YbI3(THF)(3)

Men´s experiences of using anabolic androgenic steroids

Purpose: Anabolic androgenic steroids (AAS) are used by men for their aesthetic and performance-enhancing effects and are associated with risk for side effects. Our research aims to deepen knowledge and understanding of men´s experiences of using AAS. Method: This phenomenological study is based on the reflective lifeworld research approach. Lifeworld interviews were conducted with twelve men about their experiences of using AAS. Results: By using AAS, men strive towards a muscular, strong and athletic ideal. Self-imposed demands, self-discipline and performance accelerate male physical development. The perfect male body ideal thus attained is fragile from both an existential and a biological perspective. The perfect self-image can easily be shattered by adversity. A man’s very existence may be jeopardized if the use of AAS is revealed to others or if the body is let down by illness. Conclusions: Men´s use of AAS is a complex phenomenon. It partly concerns a traditional view of masculinity that is reflected in the community. It requires both broad and deep knowledge and understanding to be able to meet men using AAS in their problems and vulnerability; a meeting that is hampered by their low trust in healthcare, and by the fact that AAS are illegal. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Catalytic Iodination of the Aliphatic C–F Bond by YbI₃(THF)₃: Mechanistic Insight and Synthetic Utility

A facile iodination protocol of unactivated alkyl fluorides using catalytic amounts of YbI₃(THF)₃ in the presence of iodotrimethylsilane as a stoichiometric fluoride trapping agent is presented. ¹H NMR spectroscopy demonstrates a two-step catalytic cycle where TMSI regenerates active YbI₃(THF)₃. Finally, the catalytic reaction is extended into a one-pot procedure to demonstrate a potential application of the method. Overall, the findings present a distinct strategy for C–F bond transformations in the presence of catalytic YbI₃(THF)₃