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Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors using molecular modelling, a cross-docking and correlation study was performed. A series of novel 1-(3-(3-hydroxy-4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-ones were synthesized from this model and screened for their antitubercular activity against M. tuberculosis H37Rv. Compound PYN-8 showed good antitubercular activity on M. tuberculosis H37Rv (MIC = 4–7 µM) and Mycobacterium bovis (% inhibition at 10 µM = 95.91%). Cytotoxicity of all the synthesized derivatives was assessed using various cell lines, and they were found to be safe. Structure of PYN-8 was also confirmed by single-crystal X-ray diffraction. The molecular modelling studies also corroborated the biological activity of the compounds. Further, in silico findings revealed that all these tested compounds exhibited good ADME properties and drug likeness and thus may be considered as potential candidates for further drug development. [ABSTRACT FROM AUTHOR]

Ochraceopetalin (1), a mixed-biogenetic salt compound and its component 2 were isolated from the culture broths of a marine-derived fungus, Aspergillus ochraceopetaliformis. Based on combined spectroscopic and chemical analyses, the structure of 1 was determined to be a sulfonated diphenylether-aminol-amino acid ester guanidinium salt of an unprecedented structural class, while 2 was determined to be the corresponding sulfonated diphenylether. Ochraceopetaguanidine (3), the other guanidine-bearing aminol amino acid ester component, was also prepared and structurally elucidated. Compound 1 exhibited significant cytotoxicity against K562 and A549 cells.

The nonylphenol-degrading bacterium Sphingomonas sp. strain NP5 has a very unique monooxygenase that can attack a wide range of 4-alkylphenols with a branched side chain. Due to the structural similarity, it can also attack bisphenolic compounds, which are very important materials for the synthesis of plastics and resins, but many of them are known to or suspected to have endocrine disrupting effects to fish and animals. In this study, to clarify the substrate specificity of the enzyme (NmoA) for bisphenolic compounds, degradation tests using the cell suspension of Pseudomonas putida harboring the nonylphenol monooxygenase gene (nmoA) were conducted. The cell suspension degraded several bisphenols including bisphenol F, bisphenol S, 4,4′-dihydroxybenzophenone, 4,4′-dihydroxydiphenylether, and 4,4′-thiodiphenol, indicating that this monooxygenase has a broad substrate specificity for compounds with a bisphenolic structure.

Abstract Organic wide bandgap semiconductor is a hot research topic in optoelectronic fields. In this work, a series of diphenylether-, 9,9-biphenylfluorene- and tetraphenylsilane-centered wide bandgap materials are designed and synthesized. Comprehensive experiments and theoretical calculations are conducted to investigate their intrinsic thermal stability, photophysical property, electrochemical behavior and device performance, aiming at exploring the potentials of oxygen, sp3-hybridized carbon and silicon atoms for wide bandgap materials. They all can interrupt molecular conjugation to generate wide bandgaps. By modification of appropriate donor and acceptor, relatively high triplet energy level (E T) can be obtained in the resulting materials. Quantum chemical calculations indicate the sort of triplet energy levels of N-carbazole > fluorene > benzonitrile, which fully supports the experimental results. Tetraphenylsilane-based materials display lower LUMO levels than corresponding diphenylether- and 9,9-biphenylfluorene-centered materials owing to the dπ-pπ conjugation. Among them, DCzSiPy/FIrpic doped device gives the best device performance with maximum current efficiency of 35.6 cd/A and maximum external quantum efficiency of 16.8%, demonstrating the superiority of tetraphenylsilane skeleton. 9,9-Biphenylfluorene-based doped devices have comparable efficiencies with tetraphenylsilane-hosted ones, meaning 9,9-biphenylfluorene unit also can be a good constructing skeleton for wide bandgap host materials. Graphical abstract Their potentials of diphenylether-, 9,9-biphenylfluorene- and tetraphenylsilane-centered wide bandgap hosts for FIrpic are investigated. Tetraphenylsilane-based doped devices give better performance demonstrating the superiority of tetraphenylsilane skeleton. Image 1 Highlights • A series of different wide bandgap host materials for FIrpic are investigated. • Tetraphenylsilane-based hosts display lower LUMO levels owing to dπ-pπ conjugation. • DCzSiPy/FIrpic doped device possesses the highest EQE of 16.8%. [ABSTRACT FROM AUTHOR]

Abstract: Two series of arylethers with different substituents placed at para positions to the etherereal oxygens were synthesized and incorporated into poly-vinylchloride (PVC) matrix membranes to study their ionophoric potential in potentiometric ISEs. The electrodes based on diphenyl ethers (Ia and Ib) and triphenyl ethers (IIa, IIb and IIc) showed high selectivity for Fe2+ and Ca2+, respectively. The electro-analytical studies on these electrodes revealed that the ionophores with hydroxymethyl group (Ib and IIb) exhibited the best potentiometric characteristics. The membrane with optimized composition; PVC: o-NPOE: ionophore (Ib): NaTPB as 33:61:3:3 (wt%) worked with a Nernstian slope of 28.1 mV per decade of Fe2+ activity and a detection limit of 3.9 × 10−7 M while the membrane (IIb) with an optimised composition of 33:60:4:3 exhibited a Nernstian slope of 29 mV per decade and a detection limit of 3.2 × 10−7 M for Ca2+. Response time of the electrodes was recorded as 20 and 15 s, respectively for di and tri phenyl derivatives with a life time of at least 4 months without any measurable divergence in response characteristics over a wide pH range of 4-10. Theoretical calculations (DFT) for the host-guest interactions supported the observed substituent influence on the selectivity of ISEs. The ionophores have advantages over the earlier reported ones because of their simple synthesis, stability and easy modification of oxygen binding ability resulting from substitution.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Two new metabolites, diorcinolic acid (1) and β-d-glucopyranosyl aspergillusene A (8), together with six diphenylethers (2–7), a diketopiperazine (9), a chromone (10) and a xanthone (11) were isolated from the fungus Aspergillus sydowii derived from the marine sponge Stelletta sp. The planar structures and their relative configurations were elucidated by analysing 1D, 2D NMR and HRESIMS data. Compound 8 is the first glycoside of phenolic bisabolane sesquiterpenes. Compounds 1 and 8 exhibited mild cytotoxicity against KB (human nasopharyngeal carcinoma cells), HepG2 (human liver cancer cells) and HCT 116 (human colon cancer cells). All compounds were evaluated for antibacterial activity and their abilities to suppress LPS-induced nitric oxide (NO) production. Compounds 2 and 4–7 showed mild antibacterial activity against human pathogen Staphylococcus aureus and fish pathogens Streptococcus iniae and Vibrio ichthyoenteri, and compounds 4 and 7 weakly suppressed NO production. [ABSTRACT FROM AUTHOR]

Background & objectives: DPE-28, a substituted diphenyl ether [2,6-ditertiarybutyl phenyl-2',4'-dinitro phenyl ether) was reported to exhibit promising insect growth regulating activity against Culex quinquefasciatus, the vector of lymphatic filariasis. A controlled release formulation (CRF) of DPE-28 has been developed to control Cx. quinquefasciatus in its breeding habitats. Toxicity of DPE-28, safety to non-target mosquito predators and the release profile of the CRF of DPE-28 are studied and discussed. Methods: The acute oral and dermal toxicity was tested in male and female Wistar rats as per the Organization for Economic Cooperation and Development (OECD) guidelines 425 and 402 respectively. The toxicity of DPE-28 to non-target predators was tested as per the reported procedure from this laboratory. The CRF of DPE-28 was prepared by following the reported procedure developed at this laboratory earlier. The concentration of DPE-28 released from the CRF was monitored by HPLC by constructing a calibration graph by plotting the peak area in the Y-axis and the concentration of DPE-28 in the X-axis. Results: DPE-28 has been tested for acute oral toxicity and found to be moderately toxic with LD50 value of 1098 mg/kg body weight (b.w). The results of the acute dermal toxicity and skin irritation studies reveal that DPE-28 is safe and non-irritant. DPE-28 when tested at 0.4 mg/litre against non-target mosquito predators did not produce any mortality. The release profile of the active ingredient DPE-28 from the CRF by HPLC technique showed that the average daily release (ADR) of DPE-28 ranged from 0.07 to 5.0 mg/litre during first four weeks. Thereafter the matrix started eroding and the ADR ranged from 5 to 11 mg/litre during the remaining 5 wk. The cumulative release of active ingredient showed that > 90 per cent of the active ingredient was released from the matrix. Interpretation & conclusions: The controlled release matrix of DPE-28 was thus found to inhibit the adult emergence (>80%) of Cx. quinquefasciatus for a period of nine weeks. The CRF of DPE-28 may play a useful role in field and may be recommended for mosquito control programme after evaluating the same under field conditions. [ABSTRACT FROM AUTHOR]

Discovered 40 years ago, plant glutathione transferases (GSTs) now have a well-established role in determining herbicide metabolism and selectivity in crops and weeds. Within the GST superfamily, the numerous and plant-specific phi (F) and tau (U) classes are largely responsible for catalyzing glutathione-dependent reactions with xenobiotics, notably conjugation leading to detoxification and, more rarely, bioactivating isomerizations. In total, the crystal structures of 10 plant GSTs have been solved and a highly conserved N-terminal glutathione binding domain and structurally diverse C-terminal hydrophobic domain identified, along with key coordinating residues. Unlike drug-detoxifying mammalian GSTs, plant enzymes utlilize a catalytic serine in place of a tyrosine residue. Both GSTFs and GSTUs undergo changes in structure during catalysis indicative of an induced fit mechanism on substrate binding, with an understanding of plant GST structure/function allowing these proteins to be engineered for novel functions in detoxification and ligand recognition. Several major crops produce alternative thiols, with GSTUs shown to use homoglutathione in preference to glutathione, in herbicide detoxification reactions in soybeans. Similarly, hydroxymethylglutathione is used, in addition to glutathione in detoxifying the herbicide fenoxaprop in wheat. Following GST action, plants are able to rapidly process glutathione conjugates by at least two distinct pathways, with the available evidence suggesting these function in an organ- and species-specific manner. Roles for GSTs in endogenous metabolism are less well defined, with the enzymes linked to a diverse range of functions, including signaling, counteracting oxidative stress, and detoxifying and transporting secondary metabolites. [ABSTRACT FROM AUTHOR]

Abstract: Aclonifen belongs to the diphenylether (DPE) chemical family among which potent herbicides with a photodependent mode of action can be found. For years aclonifen has been used in several types of cultures. However its biochemical mode of action remains unclear although it was listed as a carotenoid synthesis inhibitor by the Herbicide Resistance Action Committee (HRAC). As a matter of fact, corn seedling leaves treated with 10−4 M aclonifen and maintained in the dark no longer contained carotenoids but showed an accumulation of a compound having all the characteristics of phytoene. That demonstrated aclonifen ability to inhibit the desaturases catalyzing the transformation of phytoene into carotenoids. Moreover, aclonifen (5×10−5 M) was responsible for a photodependent cell destruction (necrosis) of cucumber cotyledons typically due to protoporphyrin IX accumulation. The same phenomenon was demonstrated in aclonifen-treated etiolated corn seedlings (10−4 M) that showed an accumulation of protoporphyrin IX, reaching 62ng/g of leaf fresh mass and reactive oxygen species production under light. On these two cases (cucumber cotyledons and etiolated corn seedlings), aclonifen was acting as a typical DPE, as demonstrated by the accumulation of protoporphyrin IX. As a whole, aclonifen was shown here, to act on two different biochemical pathways including carotenoid synthesis on the one hand, as well as protoporphyrinogen oxidase, in the chlorophyll synthesis pathway, on the other for the same range of concentrations. [Copyright &y& Elsevier]

The fungus, Tritirachium sp. HKI 0317, was isolated from the Antarctic lichen Neuropogon sp. Fermentation of this strain, extraction of the culture broth, and preparative separation of produced compounds furnished 4‐carboxy‐5,5′‐dihydroxy‐3,3′‐dimethyldiphenylether (1), macrosphelide A (2), and macrosphelide J (3). The structures were elucidated on the basis of MS and NMR measurements, and the previously published data for this compounds. [ABSTRACT FROM AUTHOR]

Abstract: Zirconia-supported silicotungstic acid (15% STA) catalyst with different calcination temperatures (600–850°C) was prepared by suspending zirconium oxyhydroxide in methanol solution of STA followed by drying and calcination. These catalysts were characterized by XRD, FTIR pyridine adsorption and DRUV–vis spectroscopy. The catalysts showed both Brønsted as well as Lewis acidity and 15% STA on zirconia calcined at 750°C (15 SZ-750) had the highest Brønsted acidity. Characterization of 15 SZ-750 catalyst by Raman spectroscopy showed the presence of zirconia-anchored mono-oxotungstate as the major tungsten species present in this catalyst. These catalysts were used in benzoylation of veratrole with benzoic anhydride and 15 SZ-750 catalyst showed the highest activity. For catalyst with support calcined at different temperatures before HPA impregnation, catalytic activity decreases as the support calcination temperature increases due to the decrease in Brønsted acidity. Comparison of the catalytic activity of 15 SZ-750 with that of zirconia-supported phosphotungstic acid (15%, calcined at 750°C, 15 PZ-750) in benzoylation of veratrole with benzoic anhydride, acylation of anisole with acetic anhydride and in alkylation of diphenylether with 1-dodecene showed that 15 SZ-750 catalyst has higher activity and deactivation resistance due to its higher Brønsted acidity. The deactivated catalyst could be regenerated by calcination without appreciable loss in activity. [Copyright &y& Elsevier]

Plastic model compounds having ether linkage were reacted in sub- and supercritical water to obtain information on the optimum conditions of plastic decomposition reaction into monomeric compounds. Conversion of dinaphthylether to naphthol was attained by the reaction in 3 ml of water including basic additives at 703 K. In the reaction in supercritical water, no production of naphthalene was confirmed suggesting chemical participation of water. Diphenylether was also decomposed into phenol in the reaction in supercritical water including Na2CO3. Decomposition reactions of 1,4-diphenoxybenzene and p-phenoxyphenol were also confirmed. [Copyright &y& Elsevier]

The radiation-induced decomposition and product analysis of diphenyloxide (DPO; diphenylether), selected as a representative of the toxic polyaromatic, volatile, hydrocarbons produced by combustion of coal, was investigated in aqueous solution. In the presence of air an initial degradation yield, Gi(-DPO)0=4.6 was obtained. Phenol (Gi=1.3) appeared to be the major decomposition product in addition to a number of hydroxy-compounds as well as a mixture of aldehydes and carboxylic acids. DPO as well as the resulting products can be decomposed at an absorbed radiation dose of about 5 kGy.By performing analogous studies in solution saturated with N2O an initial yield of Gi(-DPO)=5.0 and similar radiolytic products were found. Again phenol (Gi=1.5) is observed as the main product. In this case a much lower radiation dose (∼2.5 kGy) is found to be sufficient for the decomposition of DPO and its radiolytic products. Most likely reaction mechanisms are presented for explanation of the observed products. [Copyright &y& Elsevier]

Diphenylether (DPE) was efficiently hydrolyzed into phenol (up to 58 mol%), using Lewis acids, such as boron trifluoride (BF3) and Ni(BF4)2, in supercritical water (SCW) at 380 °C. The side-reactions were insignificant, and BF3 was found to be nearly twice as effective, than HBF4 under the same conditions. Cleavage of DPE in supercritical organic solvents, such as 2,2,2-trifluoroethanol and trifluoroacetic acid, with BF3 at 250 °C, was less successful and accompanied by Friedel-Crafts side-reactions. However, >25 mol% of DPE was cleaved to phenyl trifluoroacetate in supercritical trifluoroacetic acid with equimolar BF3 at 250 °C/1 h. [Copyright &y& Elsevier]

Ochraceopetalin (1), a mixed-biogenetic salt compound and its component 2 were isolated from the culture broths of a marine-derived fungus, Aspergillus ochraceopetaliformis. Based on combined spectroscopic and chemical analyses, the structure of 1 was determined to be a sulfonated diphenylether-aminol-amino acid ester guanidinium salt of an unprecedented structural class, while 2 was determined to be the corresponding sulfonated diphenylether. Ochraceopetaguanidine (3), the other guanidine-bearing aminol amino acid ester component, was also prepared and structurally elucidated. Compound 1 exhibited significant cytotoxicity against K562 and A549 cells. [ABSTRACT FROM AUTHOR]

The microbial degradation of hard coal implies the cleavage of diaryl ether linkages in the coal macromolecule. We investigated the biodegradation of diphenylether as a model compound representing this substructure of coal. A bacterial strain isolated from soil and identified as Pseudomonas cepacia, was able to grow with diphenylether as sole source of carbon. During microbial growth, three metabolites were detected in the culture supernatant by high pressure liquid chromatography. As product of ring hydroxylation and subsequent rearomatization, 2,3-dihydroxydiphenylether was identified by UV, mass and nuclear magnetic resonance spectrometry and gas chromatography analyses. The cleavage of the ether linkage led to the formation of phenol and 2-pyrone-6-carboxylic acid, the latter being not further degraded by Pseudomonas cepacia. The possible cleavage mechanism of the ether linkage is discussed. [ABSTRACT FROM AUTHOR]

A study was carried out in a nylon producing plant to determine exposure to Dowtherm A from frequently occurring leaks in the heating system. The daily exposure to both diphenyl and diphenylether of 20 workers was determined over seven consecutive days. Urine samples before and after the daily eight-hour workshift were obtained and analysed spectro-fluorimetrically on hydroxydiphenyl. Urine concentration of creatinin was used as a correction factor for dilution. No correlation was found between the increase of urinary hydroxydiphenyl during the workshift and the eight-hour average exposure to diphenyl for the individual workers. This could be explained by the small variance of the daily exposure of each worker. Averaging, however, for each worker both exposure values and increases of urinary hydroxydiphenyl over 7 d, resulted in an explained variance of 72.5% using regression techniques. No influence of smoking was found. [ABSTRACT FROM AUTHOR]

Abstract: In search of a next generation molecule to the novel wake promoting agent modafinil, a series of diphenyl ether derived wakefulness enhancing agents (in rat) was developed. From this work, racemic compound 16 was separated into its chiral enantiomers to profile them individually. [Copyright &y& Elsevier]

The nonylphenol-degrading bacterium Sphingomonas sp. strain NP5 has a very unique monooxygenase that can attack a wide range of 4-alkylphenols with a branched side chain. Due to the structural similarity, it can also attack bisphenolic compounds, which are very important materials for the synthesis of plastics and resins, but many of them are known to or suspected to have endocrine disrupting effects to fish and animals. In this study, to clarify the substrate specificity of the enzyme (NmoA) for bisphenolic compounds, degradation tests using the cell suspension of Pseudomonas putida harboring the nonylphenol monooxygenase gene (nmoA) were conducted. The cell suspension degraded several bisphenols including bisphenol F, bisphenol S, 4,4′-dihydroxybenzophenone, 4,4′-dihydroxydiphenylether, and 4,4′-thiodiphenol, indicating that this monooxygenase has a broad substrate specificity for compounds with a bisphenolic structure. [ABSTRACT FROM AUTHOR]

The enoyl-acyl carrier protein (ACP) reductase (ENR) is a key enzyme within the bacterial fatty-acid synthesis pathway. It has been demonstrated that small-molecule inhibitors carrying the diphenylether (DPE) scaffold bear a great potential for the development of highly specific and effective drugs against this enzyme class. Interestingly, different substitution patterns of the DPE scaffold have been shown to lead to varying effects on the kinetic and thermodynamic behavior toward ENRs from different organisms. Here, we investigated the effect of a 4'-pyridone substituent in the context of the slow tight-binding inhibitor SKTS1 on the inhibition of the Staphylococcus aureus enoyl-ACP-reductase saFabI and the closely related isoenzyme from Mycobacterium tuberculosis , InhA, and explored a new interaction site of DPE inhibitors within the substrate-binding pocket. Using high-resolution crystal structures of both complexes in combination with molecular dynamics (MD) simulations, kinetic measurements, and quantum mechanical (QM) calculations, we provide evidence that the 4'-pyridone substituent adopts different tautomeric forms when bound to the two ENRs. We furthermore elucidate the structural determinants leading to significant differences in the residence time of SKTS1 on both enzymes.

Background: One of the most successful reagents used in the synthesis of the reactive enaminone is DMF-DMA, but it is very expensive with harmful effects on the human health and reacts with special compounds to generate the enaminone such as active methylene centers., Aim: In this article, we synthesized a new ketenaminal by simple method with inexpensive reagents (through desulfurization in diphenylether)., Methods: Thus, a novel reactive ketenaminal (enaminone) was synthesized from the desulfurization of 2-((2-(4-chlorophenyl)-2-oxoethyl)thio)-5,7-bis(4-methoxyphenyl)pyrido[2,3-d]pyrimidin- 4(3H)-one with diphenylether. The starting keteneaminal was coupled with diazotized anilines via the known coupling conditions to give a new series of 2-(4-chlorophenyl)-1-(2-(arylhydrazono)-2- oxoethyl)-5,7-bis(4-methoxy-phenyl)pyrido[2,3-d]pyrimidin-4(1H)-ones., Results: The structures of the new compounds were elucidated based on their IR, 1H-NMR, 13CNMR, and Mass spectra. Moreover, the potency of these compounds as antimicrobial agents has been evaluated. The results showed that some of the products have high activity nearly equal to that of the used standard antibiotic. Additionally, the docking study was done to get the binding mode of the synthesized compounds with the binding site of the DHFR enzyme. The results of molecular docking of the synthesized arylhydrazono compounds are able to fit in DHFR binding site with binding energies ranging from -4.989 to -8.178 Kcal/mol., Conclusion: Our goal was achieved in this context by the synthesis of new ketenaminal from inexpensive reagents, which was utilized in the preparation of bioactive arylhydrazone derivatives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.