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

Ruthenium-Catalyzed E-Selective Alkyne Semihydrogenation with Alcohols as Hydrogen Donors

Selective direct ruthenium-catalyzed semihydrogenation of diaryl alkynes to the corresponding E-alkenes has been achieved using alcohols as the hydrogen source. The method employs a simple ruthenium catalyst, does not require external ligands, and affords the desired products in > 99% NMR yield in most cases (up to 93% isolated yield). Best results were obtained using benzyl alcohol as the hydrogen donor, although biorenewable alcohols such as furfuryl alcohol could also be applied. In addition, tandem semihydrogenation-alkylation reactions were demonstrated, with potential applications in the synthesis of resveratrol derivatives

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

3,3-Dimethyl-1,2,3,4-tetra­hydro­cyclo­penta­[b]indole-1,2-dione (bruceolline E)

The title compound, C13H11NO2, crystallizes with two mol­ecules in the asymmetric unit. The crystal packing is stabilized by N—H⋯O hydrogen bonds, which link the mol­ecules into chains along [10], and weak C—H⋯O inter­actions

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

Encumbered by vulnerability and temporality - the meanings of trigger situations when learning to live with diabetes

AIMS AND OBJECTIVES: The aim of the study was to illuminate the meanings of trigger situations experienced in everyday life when learning to live with diabetes. BACKGROUND: Adults become active learners when faced with situations they do not know how to manage, triggering a need to understand something in a different way than before. Knowing more about experiential learning for persons living with diabetes is important for understanding how learning can be supported by health care. DESIGN: A life-world approach with a phenomenological hermeneutical method, inspired by the philosophy of Paul Ricoeur. METHODS: This method was used for interpreting transcriptions of interviews and consists of three stages: naïve understanding, structural analysis and a comprehensive understanding. Participants (n = 13), with either type I or type II diabetes, were interviewed on three different occasions over a three-year period after being diagnosed with diabetes. RESULTS: When learning to live with diabetes, the meanings of trigger situations were described as 'the unpredictable body heightens insecurity with awareness of one's own dependability', 'losing control in unsustainable situations' and 'encumbered by vulnerability and temporality in earlier familiar situations'. CONCLUSION: The meanings of trigger situations were to lose the smooth, unreflected way of managing an everyday life situation, interlaced with feelings of lost control of how to live with new insights of being vulnerable. Trigger situations meant an opportunity for learning, as well as being demanding, unplanned and with limited freedom of choice. Trigger situations presented life and body as unpredictable. RELEVANCE TO CLINICAL PRACTICE: If healthcare professionals can identify the worries and questions raised in trigger situations, knowledge gaps can be identified and reflected on to stimulate learning

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