Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ring-Closure Mechanisms Mediated by Laccase to Synthesize Phenothiazines, Phenoxazines, and Phenazines.

ABSTRACT: The green and environmentally friendly synthesis of highly valuable organic substances is one possibility for the utilization of laccases (EC 1.10.3.2). As reactants for the herein described syntheses, different o-substituted arylamines or arylthiols and 2,5-dihydroxybenzoic acid and its derivatives were used. In this way, the formation of phenothiazines, phenoxazines, and phenazines was achieved in aqueous solution mediated by the laccase of Pycnoporus cinnabarinus in the presence of oxygen. Two types of phenothiazines (3-hydroxy- and 3-oxo-phenothiazines) formed in one reaction assay were described for the first time. The cyclization reactions yielded C-N, C-S, or C-O bonds. The syntheses were investigated with regard to the substitution pattern of the reaction partners. Differences in C-S and C-N bond formations without cyclization are discussed.

SUBMITTER: Hahn V

PROVIDER: S-EPMC7315418 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Ring-Closure Mechanisms Mediated by Laccase to Synthesize Phenothiazines, Phenoxazines, and Phenazines.

Hahn Veronika V Mikolasch Annett A Weitemeyer Josephine J Petters Sebastian S Davids Timo T Lalk Michael M Lackmann Jan-Wilm JW Schauer Frieder F

ACS omega 20200608 24

The green and environmentally friendly synthesis of highly valuable organic substances is one possibility for the utilization of laccases (EC 1.10.3.2). As reactants for the herein described syntheses, different o-substituted arylamines or arylthiols and 2,5-dihydroxybenzoic acid and its derivatives were used. In this way, the formation of phenothiazines, phenoxazines, and phenazines was achieved in aqueous solution mediated by the laccase of Pycnoporus cinnabarinus in the presence ...[more]

PMID: 32596570

Similar Datasets

-Back-to-back mechanisms drive actomyosin ring closure during Drosophila embryo cleavage.

Project description:Contraction of actomyosin rings during cytokinesis is typically attributed to actin filaments sliding toward each other via Myosin-2 motor activity. However, rings constrict in some cells in the absence of Myosin-2 activity. Thus, ring closure uses Myosin-2-dependent and -independent mechanisms. But what the Myosin-2-independent mechanisms are, and to what extent they are sufficient to drive closure, remains unclear. During cleavage in Drosophila melanogaster embryos, actomyosin rings constrict in two sequential and mechanistically distinct phases. We show that these phases differ in constriction speed and are genetically and pharmacologically separable. Further, Myosin-2 activity is required for slow constriction in "phase 1" but is largely dispensable for fast constriction in "phase 2," and F-actin disassembly is only required for fast constriction in phase 2. Switching from phase 1 to phase 2 seemingly relies on the spatial organization of F-actin as controlled by Cofilin, Anillin, and Septin. Our work shows that fly embryos present a singular opportunity to compare separable ring constriction mechanisms, with varying Myosin-2 dependencies, in one cell type and in vivo.

| S-EPMC5100295 | biostudies-literature

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction.

Project description:Fused pyrazole ring systems are common structural motifs of numerous pharmaceutically important compounds. Nevertheless, access to derivatives of the aromatic 2H-furo[2,3-c]pyrazole ring system is still quite limited, and their chemistry and functional properties remain largely underexplored. The current study investigates routes to construct this system from easily accessible starting materials using metal-catalyzed reactions. A simple and efficient procedure to access the 2H-furo[2,3-c]pyrazole ring system was developed by employing the silver(I) ion-mediated ring-closure reaction of 4-alkynyl-3-hydroxy-1-phenyl-1H-pyrazoles as a key step. The required intermediate hydroxyalkynyl substrates for this reaction were prepared by a Pd-catalyzed coupling of 4-iodo-1-phenyl-1H-pyrazol-3-ol with ethyne derivatives. The structures of the obtained target compounds were unequivocally confirmed by detailed 1H, 13C and 15N NMR spectroscopic experiments, HRMS and a single-crystal X-ray diffraction analyses. This silver(I)-mediated 5-endo-dig cyclization of readily available 4-alkynyl-3-hydroxy-1H-pyrazoles can be used as an efficient method to access many novel 2,5-disubstituted 2H-furo[2,3-c]pyrazoles.

| S-EPMC6423569 | biostudies-literature

Substituent Effects on the N-H Bond Dissociation Enthalpies, Ionization Energies, Acidities, and Radical Scavenging Behavior of 3,7-Disubstituted Phenoxazines and 3,7-Disubstituted Phenothiazines.

Project description:The substituent effects on the N-H bond dissociation enthalpies (BDE), ionization energies (IE), acidities (proton affinity, PA), and radical scavenging behavior of 3,7-disubstituted phenoxazines (PhozNHs) and 3,7-disubstituted phenothiazines (PhtzNHs) were determined using density functional theory, with the M05-2X functional in conjunction with the 6-311++G(d,p) basis set. These thermochemical parameters calculated in both gas phase and benzene solution with respect to the changes in several different substituents including halogen, electron-withdrawing, and electron-donating groups at both 3 and 7 positions in both PhozNHs and PhtzNHs systems were analyzed in terms of the inherent relationships between them with some quantitative substituent effect parameters. The kinetic rate constants of hydrogen-atom exchange reactions between PhozNH and PhtzNH derivatives with the HOO• radical were also calculated, and the effects of the substituents on the kinetic behaviors of these reactions were thereby quantitatively evaluated.

| S-EPMC7594321 | biostudies-literature

Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia.

Project description:T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, indicating that PP2A mediates the drug's antileukemic activity. Finally, human T-ALLs treated with perphenazine exhibited suppressed cell growth and dephosphorylation of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurring identification of phenothiazines as a class of drugs with anticancer effects. Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential.

| S-EPMC3904599 | biostudies-literature

Actin-ring segment switching drives nonadhesive gap closure.

Project description:Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we demonstrate a nonadhesive gap closure model in which collective cell migration, large-scale actin-network fusion, and purse-string contraction orchestrate to restore the gap. Proliferative pressure drives migrating cells to attach onto the gap front at which a pluricellular actin ring is already assembled. An actin-ring segment switching process then occurs by fusion of actin fibers from the newly attached cells into the actin cable and defusion from the previously lined cells, thereby narrowing the gap. Such actin-cable segment switching occurs favorably at high curvature edges of the gap, yielding size-dependent gap closure. Cellular force microscopies evidence that a persistent rise in the radial component of inward traction force signifies successful actin-cable segment switching. A kinetic model that integrates cell proliferation, actin fiber fusion, and purse-string contraction is formulated to quantitatively account for the gap-closure dynamics. Our data reveal a previously unexplored mechanism in which cells exploit multifaceted strategies in a highly cooperative manner to close nonadhesive gaps.

| S-EPMC7777027 | biostudies-literature

A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.

Project description:The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi-jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon-carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6-hydroxy-5,9-diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant.

| S-EPMC5095812 | biostudies-literature

Artificial Macrocycles by Ugi Reaction and Passerini Ring Closure.

Project description:Artificial macrocycles can be convergently synthesized by a sequence of an Ugi multicomponent reaction (MCR) followed by an intramolecular Passerini MCR used to close the macrocycle. Significantly, in this work, the first intramolecular macrocyclization through a Passerini reaction is described. We describe 21 macrocycles of a size of 15-20. The resulting macrocyclic depsipeptides are model compounds for natural products and could find applications in drug discovery.

| S-EPMC6280654 | biostudies-other

Signalling mechanisms and agricultural applications of (Z)-3-hexenyl butyrate-mediated stomatal closure.

Project description:Biotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Furthermore, stomata are the main entry point for several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds. Green leaf volatiles, which are commonly produced across different plant species after tissue damage, comprise an important group within volatile organic compounds. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Through different genetic, pharmacological, and biochemical approaches, we here uncover that HB perception initiates various defence signalling events, such as activation of Ca2+ permeable channels, mitogen-activated protein kinases, and production of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species. Furthermore, HB-mediated stomata closure was found to be independent of abscisic acid biosynthesis and signalling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance against Phytophthora spp. and Pseudomonas syringae infection in potato and tomato plants, respectively. Taken together, our results provide insights into the HB signalling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and propose HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.

| S-EPMC10794947 | biostudies-literature

Ring closure activates yeast ?TuRC for species-specific microtubule nucleation.

Project description:The ?-tubulin ring complex (?TuRC) is the primary microtubule nucleator in cells. ?TuRC is assembled from repeating ?-tubulin small complex (?TuSC) subunits and is thought to function as a template by presenting a ?-tubulin ring that mimics microtubule geometry. However, a previous yeast ?TuRC structure showed ?TuSC in an open conformation that prevents matching to microtubule symmetry. By contrast, we show here that ?-tubulin complexes are in a closed conformation when attached to microtubules. To confirm the functional importance of the closed ?TuSC ring, we trapped the closed state and determined its structure, showing that the ?-tubulin ring precisely matches microtubule symmetry and providing detailed insight into ?TuRC architecture. Importantly, the closed state is a stronger nucleator, thus suggesting that this conformational switch may allosterically control ?TuRC activity. Finally, we demonstrate that ?TuRCs have a strong preference for tubulin from the same species.

| S-EPMC4318760 | biostudies-literature

Borane-induced ring closure reaction of oligomethylene-linked bis-allenes.

Project description:The trimethylene-linked bis-allene 3a reacts with Piers' borane [HB(C6F5)2] by a hydroboration/allylboration sequence to generate the cyclization product 5a. Its pyridine adduct was isolated and characterized by X-ray diffraction. Compound 5a undergoes a typical frustrated Lewis pair 1,2-P/B alkene addition reaction with PPh3 to give the heterobicyclic bridged olefinic zwitterionic product 9a. The tetramethylene-linked bis-allene 3b and its phenylene annulated analogue 3c react with HB(C6F5)2 to give the analogous seven-membered ring products 5b,c under mild conditions. The cyclization product 5a undergoes a series of sequential allylboration reactions with two equivalents of allene followed by ring-closure to give the four-component coupling product 12a. It undergoes FLP addition to an exo-methylene group upon treatment with PPh3. Compound 12a is oxidatively converted to the boron-free alcohol.

| S-EPMC8148058 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data