Triphenyltin(IV) compounds with naphthoquinone derivatives containing N-acetylcysteine, N-acetyl-S-(1,2-dion-4-naphthyl)cysteine (1,2-NQC), 1, and N-acetyl-S-(1,4-dion-2-naphthyl)cysteine (1,4-NQC), 2, were synthesized and characterized by elemental microanalysis, IR, multinuclear (1H, 13C, 119Sn) NMR spectroscopy as well as HR-ESI mass spectrometry. With the aim of in vitro anticancer activity determination of ligand precursors and novel synthesized organotin(IV) compounds against human cervix adenocarcinoma (HeLa), human colon carcinoma (HT-29), and melanoma carcinoma cell line (B16F10), MTT colorimetric assay method was applied. The results indicate that synthesized compounds exhibited remarkable antiproliferative activity toward all tested cell lines with IC50 in the range of 0.17 to 0.87 μM. Complex 1 showed the greatest activity against HT-29 cells, with IC50 value of 0.21 ± 0.01 μM, 119 times better than cisplatin, while complex 2 demonstrated the highest activity toward HeLa cells, IC50 = 0.17 ± 0.01 μM, which is ~26 times better than cisplatin.

BackgroundPlant extracts are increasingly investigated as potential drugs against Alzheimer's disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects.Hypothesis/PurposePycnogenol is thought to improve cognitive functions in elderly. We wanted to investigate and quantify these effects in a model system of cerebral ß-amyloidosis/AD.Study design/methodsThis study experimentally assessed the effects of Pycnogenol on AD-related pathology in a ß-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. The effects of Pycnogenol were characterized by analysing ß-amyloid (Aß) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. Aß levels were quantified using ELISA and gene expression levels of APP-processing enzymes ADAM10, BACE1 and IDE protein levels were determined by Western blot. Behavioural changes in circadian rhythm were monitored and spatial memory / cognition was assessed using a water maze test.ResultsPycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aß or the gene expression of APP-processing enzymes. The morphological analyses revealed no changes in the number of neurons, astrocytes, microglia, the myelination pattern, or the morphology of axons. Behavioural testing revealed an improvement of the spatial memory in the pre-onset treatment paradigm only.ConclusionOur results suggest to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.

Potato plants treated with the pathogen-associated molecular pattern Pep-13 mount salicylic acid- and jasmonic acid-dependent defense responses, leading to enhanced resistance against Phytophthora infestans, the causal agent of late blight disease. Recognition of Pep-13 is assumed to occur by binding to a yet unknown plasma membrane-localized receptor kinase. The potato genes annotated to encode the co-receptor BAK1, StSERK3A and StSERK3B, are activated in response to Pep-13 treatment. Transgenic RNAi-potato plants with reduced expression of both SERK3A and SERK3B were generated. In response to Pep-13 treatment, the formation of reactive oxygen species and MAP kinase activation, observed in wild type plants, is highly reduced in StSERK3A/B-RNAi plants, suggesting that StSERK3A/B are required for perception of Pep-13 in potato. In contrast, defense gene expression is induced by Pep-13 in both control and StSERK3A/B-depleted plants. Altered morphology of StSERK3A/B-RNAi plants correlates with major shifts in metabolism, as determined by untargeted metabolite profiling. Enhanced levels of hydroxycinnamic acid amides, typical phytoalexins of potato, in StSERK3A/B-RNAi plants are accompanied by significantly decreased levels of flavonoids and steroidal glycoalkaloids. Thus, altered metabolism in StSERK3A/B-RNAi plants correlates with the ability of StSERK3A/B-depleted plants to mount defense, despite highly decreased early immune responses.

Mass spectrometry (MS) is one of the primary techniques used for large-scale analysis of small molecules in metabolomics studies. To date, there has been little data format standardization in this field, as different software packages export results in different formats represented in XML or plain text, making data sharing, database deposition, and reanalysis highly challenging. Working within the consortia of the Metabolomics Standards Initiative, Proteomics Standards Initiative, and the Metabolomics Society, we have created mzTab-M to act as a common output format from analytical approaches using MS on small molecules. The format has been developed over several years, with input from a wide range of stakeholders. mzTab-M is a simple tab-separated text format, but importantly, the structure is highly standardized through the design of a detailed specification document, tightly coupled to validation software, and a mandatory controlled vocabulary of terms to populate it. The format is able to represent final quantification values from analyses, as well as the evidence trail in terms of features measured directly from MS (e.g., LC-MS, GC-MS, DIMS, etc.) and different types of approaches used to identify molecules. mzTab-M allows for ambiguity in the identification of molecules to be communicated clearly to readers of the files (both people and software). There are several implementations of the format available, and we anticipate widespread adoption in the field.

Lignin, a component of the cell walls of plants and the second most abundant biopolymer has long been regarded as disturbing substance in pulp production by paper industry. This view has changed in recent decades. Thus, lignin is increasingly regarded as an alternative to crude oil. Tuned and modified lignins have suitable properties to use them as building blocks for various applications as well as for the production of basic chemicals. By modifying lignin, its reactivity and uniformity can be increased. In addition, properties of the lignin can be changed and influenced by selective modification. By a solvent-free modification with dihydroxybenzene, aliphatic OH groups of the lignin side chain can be removed and covalent CC bonds to the aromatics can be formed. At the same time, aryl-alkyl ether cleavage occurs, which reduces the molecular weight of lignin by about one third. In addition, ongoing reactions result in the reduction in the molecular weight distribution. All this leads to a more uniform and reactive lignin which is interesting as a precursor for various applications. This work provides a deeper understanding of ongoing reactions with dihydroxybenzenes and the structure of modified lignins.

Rene Koenigs developed a tryptamine synthesis by C–H functionalization of indoles with diazoacetonitrile.Tryptamines are important endogenous signaling molecules that play a pivotal role in biochemical processes like the regulation of the sleep–wake rhythm. The closely related serotonin possesses key regulatory functions in the cardiovascular system and organ development and plays a central role as a neurotransmitter in the central nervous system. The synthesis of tryptamines is typically conducted following a classic route starting with a Mannich reaction of an indole heterocycle, followed by quaternization of the amine, nucleophilic substitution with highly toxic cyanide and final reduction. Professor Rene Koenigs (RWTH Aachen University, Germany) and co-workers previously reported on carbene transfer reactions of the underexplored and explosive diazoacetonitrile reagent. In a team effort with the groups of Junior Professor Martin J. Weissenborn (Leibniz Institute of Plant Biochemistry and Martin-Luther University Halle-Wittenberg, Germany) and Dr. Junming Ho (University of New South Wales, Sydney) iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles were developed to synthesize important precursors of tryptamines.

The functionalization of C−H bonds with non‐precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof‐of‐concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C−H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines.

Die Funktionalisierung von C‐H‐Bindungen mit Nichtedelmetallkatalysatoren ist ein wichtiges Forschungsgebiet für die Entwicklung effizienter und nachhaltiger Synthesemethoden. In diesem Artikel beschreiben wir die Entwicklung Eisenporphyrin‐katalysierter Reaktionen von Diazoacetonitril mit N‐Heterocyclen um so einen Zugang zu wertvollen Vorläufern zu Tryptaminen zu erhalten. Darüberhinaus berichten wir über experimentelle mechanistische Studien sowie über konzeptionelle Studien zu einer enzymatischen Synthese mit dem Enzym YfeX. Mit dem leicht zugänglichen FeTPPCl‐Katalysator konnten wir hoch effiziente C‐H‐Funktionalisierungsreaktionen von Indol und Indazol‐Heterocyclen zeigen. Diese Reaktionen können unter milden Reaktionsbedingungen, mit exzellenten Ausbeuten und großer Toleranz funktioneller Gruppen inklusive Anwendungen im Grammmaßstab durchgeführt werden und eröffnen so einen einzigartigen, effizienten Zugang zu Tryptaminen.

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Plants are in permanent contact with various microorganisms and are always impacted by them. To better understand the first steps of a plant’s recognition of soil-borne microorganisms, the early release of volatile organic compounds (VOCs) emitted from roots of Medicago truncatula in response to the symbiont Rhizophagus irregularis or the pathogenic oomycete Aphanomyces euteiches was analysed. More than 90 compounds were released from roots as detected by an untargeted gas chromatography-mass spectrometry approach. Principal component analyses clearly distinguished untreated roots from roots treated with either R. irregularis or A. euteiches. Several VOCs were found to be emitted specifically in response to each of the microorganisms. Limonene was specifically emitted from wild-type roots after contact with R. irregularis spores but not from roots of the mycorrhiza-deficient mutant does not make infections3. The application of limonene to mycorrhizal roots, however, did not affect the mycorrhization rate. Inoculation of roots with A. euteiches zoospores resulted in the specific emission of several sesquiterpenes, such as nerolidol, viridiflorol and nerolidol-epoxyacetate but application of nerolidol to zoospores of A. euteiches did not affect their vitality. Therefore, plants discriminate between different microorganisms at early stages of their interaction and respond differently to the level of root-emitted volatiles.