Simple electrochemical synthesis of cyclic hydroxamic acids by reduction of nitroarenes.

The electrochemical reduction of nitroarenes allows direct access to manifold nitrogen containing heterocycles. This work reports the simple and direct electro-organic synthesis of 18 different examples of 2,4-4-hydroxy-1,4-benzoxazin-3-ones in up to 81% yield. The scalability of the method was demonstrated on a gram-scale.

Bringing Light into the Dark-Overview of Environmental Impacts of Carbon Fiber Production and Potential Levers for Reduction.

Carbon fibers (CFs) are a crucial material for lightweight structures with advanced mechanical performance. However, there is still a paucity of detailed understanding regarding the environmental impacts of production. Previously, mostly singled-out scenarios for CF production have been assessed, often based on scarce transparent inventory data.

Self-Standing Metal Foam Catalysts for Cathodic Electro-Organic Synthesis.

Although electro-organic synthesis is currently receiving renewed interest because of its potential to enable sustainability in chemical processes to value-added products, challenges in process development persist: For reductive transformations performed in protic media, an inherent issue is the limited choice of metallic cathode materials that can effectively suppress the parasitic hydrogen evolution reaction (HER) while maintaining a high activity toward the targeted electro-organic reaction. Current development trends are aimed at avoiding the previously used HER-suppressing elements (Cd, Hg, and Pb) because of their toxicity. Here, this work reports the rational design of highly porous foam-type binary and ternary electrocatalysts with reduced Pb content.

Simple and scalable electrosynthesis of 1-1-hydroxy-quinazolin-4-ones.

Cathodic synthesis provides sustainable access to 1-hydroxy- and 1-oxy-quinazolin-4-ones from easily accessible nitro starting materials. Mild reaction conditions, inexpensive and reusable carbon-based electrode materials, an undivided electrochemical setup, and constant current conditions characterise this method. Sulphuric acid is used as a simple supporting electrolyte as well as a catalyst for cyclisation.

Direct Electrochemical Synthesis of 2,3-Disubstituted Quinoline N-oxides by Cathodic Reduction of Nitro Arenes.

The use of electric current in synthetic organic chemistry offers a sustainable tool for the selective reductive synthesis of quinoline N-oxides starting from easily accessible nitro compounds. The reported method employs mild and reagent-free conditions, a simple undivided cell, and constant current electrolysis set-up which provides conversion with a high atom economy. The synthesis of 30 differently substituted quinoline N-oxides was successfully performed in up to 90 % yield.

Cathodic Corrosion of Metal Electrodes-How to Prevent It in Electroorganic Synthesis.

The critical aspects of the corrosion of metal electrodes in cathodic reductions are covered. We discuss the involved mechanisms including alloying with alkali metals, cathodic etching in aqueous and aprotic media, and formation of metal hydrides and organometallics. Successful approaches that have been implemented to suppress cathodic corrosion are reviewed.

Selective HSP90β inhibition results in TNF and TRAIL mediated HIF1α degradation.

Signaling via TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Previous reports demonstrated that pro-survival signaling emanates from membrane resident TNF-R1 complexes (complex I) while only internalized TNF-R1 complexes are capable for DISC formation (complex II) and thus, apoptosis induction. Internalized TNF-R1 containing endosomes undergo intracellular maturation towards lysosomes, resulting in activation and release of Cathepsin D (CtsD) into the cytoplasm.

Combination of the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus as a new option for epi-virotherapeutic treatment of hepatocellular carcinoma.

Epigenetic therapies such as histone deacetylase inhibitors (HDACi) not only have the capability to decrease tumor cell proliferation and to induce tumor cell death but also to silence antiviral response genes. Here, we investigated whether the combination of an oncolytic measles vaccine virus (MeV) with the novel oral HDACi resminostat (Res), being in clinical testing in patients with hepatocellular carcinoma (HCC), results in an enhanced efficacy of this epi-virotherapeutic approach compared to any of the two corresponding monotherapies. When testing a panel of human hepatoma cell lines, we found (i) a significantly improved rate of primary infections when using oncolytic MeV under concurrent treatment with resminostat, (ii) a boosted cytotoxic effect of the epi-virotherapeutic combination (Res + MeV) with enhanced induction of apoptosis, and, quite importantly, (iii) an absence of any resminostat-induced impairment of MeV replication and spread.

Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene.

Background: In conjunction with posttranslational chromatin modifications, proper arrangement of higher order chromatin structure appears to be important for controlling transcription in the nucleus. Recent genome-wide studies have shown that the Estrogen Receptor-alpha (ERα), encoded by the ESR1 gene, nucleates tissue-specific long-range chromosomal interactions in collaboration with the cohesin complex. Furthermore, the Mediator complex not only regulates ERα activity, but also interacts with the cohesin complex to facilitate long-range chromosomal interactions.

Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B.

The estrogen receptor-α (ERα) determines the phenotype of breast cancers where it serves as a positive prognostic indicator. ERα is a well-established target for breast cancer therapy, but strategies to target its function remain of interest to address therapeutic resistance and further improve treatment. Recent findings indicate that proteasome inhibition can regulate estrogen-induced transcription, but how ERα function might be regulated was uncertain.

The non-steroidal anti-inflammatory drugs Sulindac sulfide and Diclofenac induce apoptosis and differentiation in human acute myeloid leukemia cells through an AP-1 dependent pathway.

Acute myeloid leukemia is a heterogeneous disease with varying genetic and molecular pathologies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to possess significant anti-proliferative potential in various cancer cells in vitro and in vivo. Hence, treatment with these agents can be utilized to study disease specific anti-proliferative pathways.

Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer.

Mammary oncogenesis is profoundly influenced by signaling pathways controlled by estrogen receptor alpha (ERalpha). Although it is known that ERalpha exerts its oncogenic effect by stimulating the proliferation of many human breast cancers through the activation of target genes, our knowledge of the underlying transcriptional mechanisms remains limited. Our published work has shown that the in vivo activity of LIM homeodomain transcription factors (LIM-HD) is critically regulated by cofactors of LIM-HD proteins (CLIM) and the ubiquitin ligase RING finger LIM domain-interacting protein (RLIM).