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Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats. [ABSTRACT FROM AUTHOR]

A-series agent A-234 belongs to a new generation of nerve agents. The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. In this article, we first assessed A-234 stability in neutral pH for subsequent experiments. Then, we determined its inhibitory potential towards human recombinant acetylcholinesterase (HssAChE; EC 3.1.1.7) and butyrylcholinesterase (HssBChE; EC 3.1.1.8), the ability of HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime to reactivate inhibited cholinesterases (ChEs), its toxicity in rats and therapeutic effects of different antidotal approaches. Finally, we utilized molecular dynamics to explain our findings. The results of spontaneous A-234 hydrolysis showed a slow process with a reaction rate displaying a triphasic course during the first 72 h (the residual concentration 86.2%). A-234 was found to be a potent inhibitor of both human ChEs (HssAChE IC50 = 0.101 ± 0.003 µM and HssBChE IC50 = 0.036 ± 0.002 µM), whereas the five marketed oximes have negligible reactivation ability toward A-234-inhibited HssAChE and HssBChE. The acute toxicity of A-234 is comparable to that of VX and in the context of therapy, atropine and diazepam effectively mitigate A-234 lethality. Even though oxime administration may induce minor improvements, selected oximes (HI-6 and methoxime) do not reactivate ChEs in vivo. Molecular dynamics implies that all marketed oximes are weak nucleophiles, which may explain the failure to reactivate the A-234 phosphorus-serine oxygen bond characterized by low partial charge, in particular, HI-6 and trimedoxime oxime oxygen may not be able to effectively approach the A-234 phosphorus, while pralidoxime displayed low interaction energy. This study is the first to provide essential experimental preclinical data on the A-234 compound. [ABSTRACT FROM AUTHOR]

5-Hydroxymethylfuran-2-carbaldehyde reacts with aliphatic 1,2-hydroxyamine oximes in methanol to form 4,5-dialkyl-substituted 2-(5-hydroxymethylfuran-5-yl)-1H-imidazol-1-ols. [ABSTRACT FROM AUTHOR]

The reactions of nitrosoalkenes, generated in situ from the corresponding α-bromooxime upon the action of a base, with electron-rich olefins were used to synthesize a series of heterocyclic compounds containing 1,2-oxazines, the expected Diels–Alder cycloadducts. The structural features of the obtained heterocyclic compounds were determined based on NMR spectra, HRMS, and X-ray structural analysis. [ABSTRACT FROM AUTHOR]

Progesterone (≥1 µM) is used in recovery of cerebral ischemia, an effect likely contributed to by cerebrovascular dilation. The targets of this progesterone action are unknown. We report that micromolar (µM) progesterone activates mouse cerebrovascular myocyte BK channels; this action is lost in β1-/- mice myocytes and in lipid bilayers containing BK α subunit homomeric channels but sustained on β1/β4-containing heteromers. Progesterone binds to both regulatory subunits, involving two steroid binding sites conserved in β1-β4: high-affinity (sub-µM), which involves Trp87 in β1 loop, and low-affinity (µM) defined by TM1 Tyr32 and TM2 Trp163. Thus progesterone, but not its oxime, bridges TM1-TM2. Mutation of the high-affinity site blunts channel activation by progesterone underscoring a permissive role of the high-affinity site: progesterone binding to this site enables steroid binding at the low-affinity site, which activates the channel. In support of our model, cerebrovascular dilation evoked by μM progesterone is lost by mutating Tyr32 or Trp163 in β1 whereas these mutations do not affect alcohol-induced cerebrovascular constriction. Furthermore, this alcohol action is effectively counteracted both in vitro and in vivo by progesterone but not by its oxime. Progesterone is used in recovery of cerebral ischemia however the mechanism of action is unknown. Authors report here that micromolar progesterone activates mouse cerebrovascular myocyte BK channels, involving two steroid binding sites. [ABSTRACT FROM AUTHOR]

Oxime reactivators of acetylcholinesterase are commonly used to treat highly toxic organophosphate poisoning. They are effective nucleophiles that can restore the catalytic activity of acetylcholinesterase; however, their main limitation is the difficulty in crossing the blood–brain barrier (BBB) because of their strongly hydrophilic nature. Various approaches to overcome this limitation and enhance the bioavailability of oxime reactivators in the CNS have been evaluated; these include structural modifications, conjugation with molecules that have transporters in the BBB, bypassing the BBB through intranasal delivery, and inhibition of BBB efflux transporters. A promising approach is the use of nanoparticles (NPs) as the delivery systems. Studies using mesoporous silica nanomaterials, poly (l-lysine)-graft-poly(ethylene oxide) NPs, metallic organic frameworks, poly(lactic-co-glycolic acid) NPs, human serum albumin NPs, liposomes, solid lipid NPs, and cucurbiturils, have shown promising results. Some NPs are considered as nanoreactors for organophosphate detoxification; these combine bioscavengers with encapsulated oximes. This study provides an overview and critical discussion of the strategies used to enhance the bioavailability of oxime reactivators in the central nervous system. [ABSTRACT FROM AUTHOR]

The review summarizes the results and prospects of studying the reactions of acetylene with secondary alkyl ketoximes containing only one C–H bond at the α-position with respect to the oxime group in superbasic medium. The selective formation of key intermediate products in the pyrrole synthesis (3H-pyrroles and 5-hydroxypyrrolines), their reactivity, and unique cascade assemblies of unexpected compounds are discussed. [ABSTRACT FROM AUTHOR]

A series of new (1S)-(+)-camphor-10-sulfonamides containing various substituents at the nitrogen atom were synthesized, and their antiviral properties against Ebola virus were evaluated using a vesicular stomatitis virus-based pseudovirus system. The reduction of the carbonyl group at the C(2) atom leads to a significant improvement in the antiviral efficacy, whereas the transformation into oxime results in the almost complete disappearance of antiviral activity. According to the evaluation of antiviral activity against natural Ebola virus, the lead compounds exhibit moderate inhibitory activity. Interactions of the lead compounds with the binding site of Ebola virus glycoprotein were studied by molecular modeling. A comparative analysis of the changes due to possible interactions of the synthesized ligands and known inhibitors with Ebola virus surface glycoprotein was carried out. [ABSTRACT FROM AUTHOR]

The modification of Fe3O4 nanomagnetic particles with inorganic and organic compounds was accomplished. The Fe3O4@SiO2@Pr-Oxime-(BuSO3H)3 as Brønsted acid was synthesized by functionalization of Fe3O4 in several steps and characterized by various techniques. Domino reaction of dimedone, anilines, ninhydrin, and malononitrile was investigated by a magnetic catalyst without using solvent at 80 °C. This method has many advantages including short reaction time, green conditions, ecofriendly, excellent yields of products, and easy separation by an external magnet. [ABSTRACT FROM AUTHOR]

In this research, synthesis of O-oxime ethers containing amino cyclic residues was described. Oximation of aromatic ketones had been followed by an O-alkylation reaction with epichlorohydrin produce the corresponding O-oxime ether adducts. The cyclization of o-phenylendiamine with O-oxime ether adducts led to synthesis of new analogues of quinoxaline compounds. The in vitro antibacterial activities of all compounds were evaluated against Escherichia coli ATTC 35218 and Staphylococcus aureus ATCC 6538 standard strains and were compared to those of tetracycline and penicillin as reference drugs. Furthermore, molecular docking studies of synthetized compounds were implemented. The results of docking studies indicated that derivatives with small substitutions such as methyl and ethyl, exhibited the highest affinity and binding to the active site of tested bacteria (E. coli Mur B (PDB ID: 2Q85) and S. aureus Gyrase B (PDB ID: 3G75)) which led to the better biological effect of these compounds. [ABSTRACT FROM AUTHOR]

Among the main contributors of water pollution are heavy metals. By being a component of the structure of enzymes, these metals, which are extremely harmful to both human health and the environment, exhibit toxic effects in living things. In this work, we aimed to prepare three phenolic-oxime derivatives (T1-oxime/T3-oxime) for liquid–liquid extraction of Cu(II) ions. The phenolic-oximes (T1-oxime/T3-oxime) were characterized by FT-IR, 1H-NMR and UV–Vis spectroscopy and the element percentages in their structures were determined by elemental analysis. Synthesized oxime compounds were subjected to liquid–liquid extraction of Cu(II) ion from the aqueous solution. The effect of pH, time and initial metal ion concentration on the extraction of Cu(II) ion was investigated. Within a short time (less than 30 min), all three oxime compounds showed 80% extraction of Cu(II) ion at pH = 4. The substitute groups at the meta position with respect to the oxime group affected the extraction of Cu(II) ion at pH = 1–2 range. The compounds were also found showed very quick extraction Cu(II) from aqueous solution to the organic phase (CHCl3) via coordination to the phenolic oxime compounds. Finally, the oxime compounds showed highly selective Cu(II) extraction in the presence of an interfering Pb(II), Ni(II) and Fe(II) ions. [ABSTRACT FROM AUTHOR]

Twelve new 2,2′-bi(1,2,4-oxadiazole) derivatives containing heterocyclic and long-chain substit-uents have been synthesized by the condensation of aldehyde azines and oximes. In silico studies of these compounds revealed their good drug likeness and drug score. Some of the synthesized compounds showed moderate to excellent larvicidal activity. [ABSTRACT FROM AUTHOR]

The article studied the structural features of solid dispersions of pinostrobin oxime with arabinogalactan, disodium salt of glycyrrhizic acid, polyvinylpyrrolidone and basic magnesium carbonate obtained by mechanochemical treatment. The obtained complexes of pinostrobin oxime with arabinogalactan, disodium salt of glycyrrhizic acid, polyvinylpyrrolidone, and basic magnesium carbonate have increased water solubility in comparison with the initial pinostrobin oxime. The thermal effects of pinostrobin oxime and its complex compounds have been studied by differential scanning calorimetry. At the same time, on the DSC-curve, the melting peak of solid dispersions of pinostrobin oxime with disodium salt of glycyrrhizated acid and pinostrobin oxime with arabinogalactan is not displayed, which is associated with the intermolecular interaction of the components of the complex, where the molecule of pinostrobin oxime forms a bond with a complex formation agent during mechanochemical treatment. The complex of pinostrobin oxime with magnesium carbonate is not formed, as evidenced by the thermal curve, where the melting of the sample begins at 182°C, and complete destruction occurs at a temperature of 782°C, which is similar to the melting peak of the initial pinostrobin oxime. The results of studying intermolecular bonds in complexes of pinostrobin oxime by the method of NMR-relaxation indicate that the times of spin–lattice and spin–spin relaxation are very sensitive to intermolecular interaction and to the mobility of diffusion of molecules. [ABSTRACT FROM AUTHOR]

The first and only work on the electrophilic amination of diarylcadmium reagents was published by our group. Herein we give the detailed results on this subject. We prepared 12 oximes and reacted them with diarylcadmiums as aminating agents to observe the effect of oxime's structure on the amination reaction. The results showed that the success of electrophilic amination of diarylcadmium reagents with oxime sulfonates is strongly influenced by the structure of the oxime. Based on the results of our research, we decided that O-substituted acetone oxime derivatives containing a suitable leaving group are the most suitable amination reagents for the high yield of amine. [ABSTRACT FROM AUTHOR]

Background: Here we report a new selenium-based heterogeneous catalyst, which was prepared from the immobilization of diphenyl diselenide on amine-functionalized Santa Barbara Amorphous-15 (SBA-15). The catalyst characterization study has been confirmed by different analysis methods including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction patterns (XRD), field-emission scanning electron microscopy (FE-SEM), and Brunauer–Emmett–Teller (BET) surface area analysis. Results: The newly designed catalyst was successfully applied in the green dehydration reaction of oximes to corresponding nitriles in the presence of hydrogen peroxide/air. To demonstrate the role of the catalyst in this study, the model reaction was also carried out in the absence of the catalyst and a trace yield of the relevant product was achieved. Conclusion: In this way, a series of nitrile derivatives were obtained with 72–96% yields, also, the catalyst could be separated easily and recycled for four consecutive runs with no obvious drop in catalytic activity. [ABSTRACT FROM AUTHOR]

The reaction of cobalt(ɪɪ) chloride with p-Br-benzoyl-β-(piperidin-1-yl)propioamid-oxime (Linit) in methanol leads to the hydrolysis of the ligand at the -OCO- ester bond and the formation of the mixed-valence hexanuclear ionic complex [CoII2CoIII4(HL)4(L)2(O)-(Cl)4]Cl2•4CH3OH (1) (L is β-(piperidin-l-yl)propioamidoxime). According to the X-ray diffraction data, the ligand (L) in 1 is coordinated to the complexing agent in different modes: the μ3-bridging-chelating mode (involving deprotonated amino groups) and the μ2- and μ3-bridging-chelating modes in the case of a coordinated amino group. Two cobalt atoms of the hexanuclear metal core have a tetrahedral coordination geometry (CoIIN2Cl2; CNCoII = 4), whereas the other four cobalt atoms are in an octahedral coordination environment of nitrogen and oxygen atoms forming the polyhedra of composition CoIIIO3N3 and CoIIIO4N2 (CNCoIII = 6). The evaluation of the in vitro biological activity of 1 against the non-pathogenic (virulent H37Rv model) mycobacterial strain of Mycolicibacterium smegmatis showed an increase in the efficiency of complex 1 by more than 4–12 times compared to the previously studied CoII,III complexes. [ABSTRACT FROM AUTHOR]

The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242. [ABSTRACT FROM AUTHOR]

A series of substituted imidazo[1,2-a]pyridines were accessed by the reaction of triterpene oximes with 2-aminopyridine under the conditions of microwave synthesis. The structures of the new compounds were confirmed by 1D and 2D NMR spectra, as well as by X-ray structural analysis. [ABSTRACT FROM AUTHOR]

O- and N-propylamino-derivatives of betulin and betulonic acid oxime and methyl ester were synthesized. Their antitumor activity against a panel of 60 human cancer cell lines was studied. Two betulin derivatives, 3β-hydroxy- 4 and 3β-O-(3-propylamino)-28-O-(3,6-diaminohexyl)lupa-20(29)-ene 5, exhibited antitumor activity against most of 60 cancer cell lines of nine different human tumor types. They were more active than doxorubicin against HCT-15 colon cancer and NCI/ADR-RES ovary cancer cells. [ABSTRACT FROM AUTHOR]

2,3-Secolupane aldehydonitriles with an isopropyl fragment were synthesized via Beckman fragmentation of ring A of triterpene α-hydroxyoximes obtained from dihydrobetulonic acid and its methyl ester. Redox transformation of the aldehydonitriles at C-3 led to the formation of the corresponding 3-hydroxy- and 3-carboxy-derivatives. The MTT assay found that only the triterpene oximes possessed moderate cytotoxic activity against HCT 116, RD TE32, MS, and PC-3 tumor cells (IC50 27.8–61.7 μM) among the synthetic products. [ABSTRACT FROM AUTHOR]

Nitrosation of lithium 1,3-diketonates bearing fluoroalkyl and aryl (or hetaryl) substituents in positions 1 and 3 results in 3-polyfluoroalkyl-1,2,3-propanetrione 2-oximes (from this point on, oximes). Under similar conditions, lithium (Z)-1,1,1-trifluoro-4-oxo-4-(thien-2-yl)-2-buten-2-olate forms a hydration product of the corresponding oxime. Nitrosation of fluoroalkyl-containing lithium 1,3-diketonates is accompanied by retro-decomposition of the initial lithium 1,3-diketonates and the target oximes (or their hydration products) followed by oxidation and hydrolysis of the reaction products. Under the GC-MS conditions, the oximes undergo partial thermal decomposition to 2-aryl(hetaryl)-2-oxoethanenitriles. An analysis of solutions of the oximes in DMSO-d6 by 1H and 19F NMR spectroscopies revealed isomerization and hydration of these compounds. The temperature ranges of stability of the oximes were determined by thermogravimetric analysis and differential thermal analysis. The molecular and crystal structures of 4,4-difluoro-1-(4-methoxyphenyl)-1,2,3-butanetrione 2-oxime and 4,4,4-trifluoro-1-(thien-2-yl)-1,2,3-butanetrione 2-oxime were determined by X-ray diffraction. [ABSTRACT FROM AUTHOR]

The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) has been synthesized in a reasonably high yield of 60%, and characterized using a variety of physical, electrochemical, spectroscopic methods and X-ray analysis. This compound belongs to the family of cyanoximes; a new subclass of oximes with the general formula NC–C(=N–OH)–R (where R is an electron-withdrawing group) which recently emerged as new biologically active compounds. This cyanoxime represents a disubstituted arylcyanoxime that was found to be a powerful inhibitor of the Carbonyl Reductase enzyme involved in the developing of resistance to anticancer treatment, and the making of cardiotoxic derivatives of anthracyclines that are currently used in medicine. The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) is a weak acid with pKa = 6.17 and does not dissociate in organic polar protic and aprotic solvents. The cyanoxime was obtained as a microcrystalline mixture of two diastereomers (anti- and syn-) and deprotonates in solutions with the formation of yellow anions which exhibit solvatochromic behavior. However, one specific diastereomer—syn—was isolated in crystalline form from a solvent system as colorless blocks overlayed with pentane ether solution in a monoclinic system in a P2/c (#13) space group with unit cell parameters: a = 8.1720(2), b = 8.8013(3), c = 13.0146(4) and β = 102.546(3); Z = 4. A single crystal was studied using filtered CuKa radiation, providing Rint value of 0.0348 from a full-sphere of reflections. A crystal structure was solved using direct methods, and well refined to R1 = 0.0459, wR2 = 0.1268 and GOF = 1.107. The studied specimen of oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO), represents a highly non-planar, rare syn-diastereomer in which the oxime fragment is positioned towards the chlorinated phenyl group. In the crystal, the compound forms a columnar structure extended along the c-direction by using slipped π–π stacking interactions. Columns are interconnected via H-bonding between the oxime OH-group and N atom of the nitrile group with the following parameters: N–H = 1.841 Å, and 169.20° N···H–O angle. No thermal interconversion of syn- into anti- diastereomer was observed upon heating of crystals of one isomer under flow of Ar. [ABSTRACT FROM AUTHOR]

Several derivatives derived from the oxime structure have been reported as potential anticancer agents in various cancers. Here, we first tested a novel oxime-containing derivative of 2-((2,4,5-trifluorobenzyl)oxy)benzaldehyde oxime (TFOBO) to evaluate its anticancer effect in myeloid leukemic cells. Compared to (2-((2,4,5-trifluorobenzyl)oxy)phenyl)methanol (TFOPM), the oxime derivative TFOBO suppresses leukemic cell growth by significantly increasing reactive oxygen species (ROS) levels and cell death. Leukemic cells treated with TFOBO displayed apoptotic cell death, as indicated by nuclear condensation, DNA fragmentation, and annexin V staining. TFOBO increases Bax/Bcl2 levels, caspase9, and caspase3/7 activity and decreases mitochondrial membrane potential. ROS production was reduced by N-acetyl-l-cysteine, a ROS scavenger, diphenyleneiodonium chloride, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, after exogenous TFOBO treatment. ROS inhibitors protect leukemic cells from TFOBO-induced cell death. Thus, our study findings suggest that TFOBO promotes apoptosis by modulating ROS and regulating NADPH oxidase activity. Collectively, the oxime-containing derivative TFOBO is a novel therapeutic drug for myeloid leukemia. [ABSTRACT FROM AUTHOR]

In search of potent antifungal agents derived from natural product 3-carene, 19 novel (Z)-3-caren-5-one oxime ethers 3a–3s were synthesized by multi-step reaction and characterized by UV–Vis, IR, NMR, ESI–MS and elemental analysis. The in vitro antifungal activity of all the target compounds was preliminarily evaluated, and the test results indicated that some of the target compounds displayed excellent inhibitory activity against R. Solani. For example, the inhibition percentages against R. Solani of compounds 3b (R = 2'–CH3), 3c (R = 3'–CH3) and 3i (R = 3'–Cl) were 98.4, 93.7 and 94.9%, respectively, which were superior or comparable to that of positive control chlorothalonil. The computational simulation study was also carried out to elucidate the structure–activity relationship (SAR) of the title compounds. Firstly, an effective and reasonable 3D-QSAR model, valuable for the optimization of the title compounds, was built by CoMFA method. In addition, DFT calculation uncovered that both 3-carene moiety and oxime ether group were the potential pharmacophores of compound 3b with the best antifungal activity. Meanwhile, molecular docking and dynamic simulation were employed for investigating the binding mode and dynamic stability of compound 3b in the Q0-site of cytochrome bc1 complex, using original ligand JZV (trifloxystrobin) as comparison. Compounds 3b (R = 2'–CH3) deserved further study as a leading compound. [ABSTRACT FROM AUTHOR]

3-Hydroxyimino derivatives of minor licorice triterpenoids possessed pronounced antiulcer activity and protected rat gastric mucosa from ulceration in indomethacin and orthophen ulcer models at a dose of 50 mg/kg. 3-Hydroxyimino-11-deoxoglycyrrhetic acid was the most active antiulcerogenic substance and was superior in activity to carbenoxolone. [ABSTRACT FROM AUTHOR]

Synthesis and biopotential investigation of organic compounds is important in both academic and industrial perspective since it help us to resolve many issues, particularly health care tasks by targeting diseases more specifically. This work was aimed at preparing Morita Baylis Hillman adducts containing keto functionality, investigating their bioactivity, and studying their transformation into oxime derivatives. Morita Baylis Hillman adducts 1-5 were synthesized from the corresponding aldehydes by treatment with methyl vinyl ketone in the presence of 1,4-diazabicyclo[2.2.2]octane at ambient temperature. All target compounds after preparation were purified with the help of column chromatography techniques and then their molecular formulas was identified through mass spectroscopy analysis and the structural formulas were elucidated from IR spectrolscopyl data. In the second part of this work, compounds 2-5 were tested against three pathogenic bacteria (E. coli, S. aureus, K. pneumoniae). Results were very significant against all the three bacteria: the zone of inhibition was 20-14 mm for compound 2, 15-10 mm for compound 3, 8-9 mm for compound 4, and 31-14 mm for compound 5. These results showed that all compounds showed significant in vitro antibacterial potential, and further in vivo studies may assist in preventing diseases associated with bacterial infections. Additionally, oximation upon the synthesized adducts were opted as a first example, and thus compound 4 was transformed into compound 6, a new oxime derivative. [ABSTRACT FROM AUTHOR]

It has of practical significance for environmental protection to find adsorbents with high efficiency, high adsorption capacity and high selectivity to treat radioactive uranium-containing wastewater. The metal–organic framework compound UiO-66-(OH)2 was synthesized by refluxing ZrCl4 and 2,5-dihydroxyterephthalic acid in N, N-dimethylformamide (DMF) at 80 ℃. UiO-66-(OH)2 was functionalized with hydroxylamine hydrochloride. UiO-66-(OH)2 amidoxime derivative obtained through chemical modification is used as adsorbent to adsorb U(VI). The result shows that the adsorption process of U(VI) on UiO-66-(OH)2 amidoxime derivative follows pseudo-second-order kinetics, the adsorption isotherm conforms to the Langmuir adsorption isotherm model. The material has good adsorption performance whose experimental results showed that the adsorption ratio of UiO-66-(OH)2 amidoxime derivative was 87.4% at C0 = 15 mg L−1, pH = 10.0 and T = 25 °C, indicating that the UiO-66-(OH)2 amidoxime derivative is a potential uranium adsorbent. [ABSTRACT FROM AUTHOR]

Due to market and legislative expectations, there is a constant need to explore new potential antimicrobial agents for functional perfumery. In this study, we evaluated the antimicrobial activity of 53 low molecular oximes and the corresponding carbonyl compounds against Escherichia coli, Enterococcus hirae, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, Aspergillus brasiliensis, Legionella pneumophila and Candida albicans. The most potent compound was α-isomethylionone oxime, which exhibited a minimum inhibitory concentration (MIC) of 18.75 µg/mL against E. hirae. The evaluation of the MICs for bacterial and fungal strains was performed for selected compounds, for example, the MIC of 2-phenylpropionaldehyde, cis-jasmone oxime, and trans-cinnamaldehyde measured against A. brasiliensis was 37.50 µg/mL. ADME-Tox (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assays were performed to assess the cytotoxicity of tested compounds. ADME-Tox indicated the safety and promising properties of selected compounds, which enables their usage as nontoxic supporting antibacterial agents. The results of the in vitro MTS assay were consistent with the ADME-Tox results. None of the compounds tested was toxic to Human Embryonic Kidney 293T (HEK293T) cells, with all cell viabilities exceeding 85%. [ABSTRACT FROM AUTHOR]

Seawater contains a large amount of uranium resources, which can meet the needs of current nuclear energy development. We designed and synthesized the oxime-modified ZIFs material, grafted the oxime group on the imidazole ligand, and improved the selective adsorption ability of uranium. In simulated seawater experiments, its adsorption effect on uranium is much higher than vanadium. The sorption could reach equilibrium with a capacity of 625 mg/g within 0.17 h at pH 5.0. Compared with the often sorbent, the oxime-modified sorbent showed faster kinetics, higher selectivity and higher extraction capacity for uranium extraction. This experiment provides an effective method for designing a highly selective sorbent for uranium, and broadens the ideas for the development of new seawater uranium extraction sorbents. [ABSTRACT FROM AUTHOR]

Methods for the preparation of pinopyridines from pinocarvone oxime or its ethers and alkenes (alkynes) using the C–H activation reaction were studied. Palladium complexes and Wilkinson's catalyst were chosen as the catalytic systems. [ABSTRACT FROM AUTHOR]

In this study, the optimum spinning conditions were determined by orthogonal experiment, and polyamide oxime nanofibers (PAO NFs) with excellent morphology and adsorption were prepared by electrospinning oxime solution. PAO NFs were characterized by SEM, FTIR, NMR and elemental analysis. The effects of time, solid–liquid ratio, pH, ionic strength, initial concentration and temperature on U(VI) adsorption on PAO NFs were studied. U(VI) adsorption on PAO NFs fitted well by the pseudo first/second-order kinetic model and Langmuir model with linear equation. The maximum adsorption was 118 mg/g. Uranyl ion was coordinated with oxime oxygen and amine nitrogen of the amidoxime group. PAO NFs is expected to extract uranium from seawater efficiently and economically. [ABSTRACT FROM AUTHOR]

The reduction of 4-oximes derived from 1β-hydroxy-, 1β,13-epoxy-, and 1,1-(ethylenedioxy)dihy-dro-quinopimaric acid methyl esters, as well as from 1β-hydroxydihydroquinopimaric acid amides, with sodium cyanotrihydroborate in the presence of titanium(III) chloride and sodium acetate afforded new 4α-amino derivatives. [ABSTRACT FROM AUTHOR]

The synthesis of oximes from aryl aldehydes was prepared using hydroxylamine hydrochloride. The obtained oxime compounds were synthesized at maximum efficiency in mineral water at room temperature. The developed method is economical, practical and environmentally friendly. All of the aldehydes were converted the oxime a method using local sources and useful for industrial applications is introduced in the literature. In this study, addition elimination reaction, one of the important reactions of organic chemistry, was carried out using local sources. With this reaction, aryl oximes were obtained from aryl aldehydes in mineral water under catalyst-free conditions. [ABSTRACT FROM AUTHOR]

Oximes, investigated as antidotes against organophosphates (OP) poisoning, are known to display toxic effects on a cellular level, which could be explained beyond action on acetylcholinesterase as their main target. To investigate this further, we performed an in vitro cell-based evaluation of effects of two structurally diverse oxime groups at concentrations of up to 800 μM, on several cell models: skeletal muscle, kidney, liver, and neural cells. As indicated by our results, compounds with an imidazolium core induced necrosis, unregulated cell death characterized by a cell burst, increased formation of reactive oxygen species, and activation of antioxidant scavenging. On the other hand, oximes with a pyridinium core activated apoptosis through specific caspases 3, 8, and/or 9. Interestingly, some of the compounds exhibited a synergistic effect. Moreover, we generated a pharmacophore model for each oxime series and identified ligands from public databases that map to generated pharmacophores. Several interesting hits were obtained including chemotherapeutics and specific inhibitors. We were able to define the possible structural features of tested oximes triggering toxic effects: chlorine atoms in combination with but-2(E)-en-1,4-diyl linker and adding a second benzene ring with substituents such as chlorine and/or methyl on the imidazolium core. Such oximes could not be used in further OP antidote development research, but could be introduced in other research studies on new specific targets. This could undoubtedly result in an overall improved wider use of unexplored oxime database created so far in OP antidotes field of research in a completely new perspective. [ABSTRACT FROM AUTHOR]

Nerve agents have experienced a resurgence in recent times with their use against civilian targets during the attacks in Syria (2012), the poisoning of Sergei and Yulia Skripal in the United Kingdom (2018) and Alexei Navalny in Russia (2020), strongly renewing the importance of antidote development against these lethal substances. The current standard treatment against their effects relies on the use of small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Despite their efficacy in reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is primarily limited to the peripheral nervous system (PNS) and, thus, provides no significant protection to the central nervous system (CNS). This lack of action in the CNS stems from their ionic nature that, on one end makes them very powerful reactivators and on the other renders them ineffective at crossing the Blood Brain Barrier (BBB) to reach the CNS. In this report, we describe the use of an iterative approach composed of parallel chemical and in silico syntheses, computational modeling, and a battery of detailed in vitro and in vivo assays that resulted in the identification of a promising, novel CNS-permeable oxime reactivator. Additional experiments to determine acute and chronic toxicity are ongoing. [ABSTRACT FROM AUTHOR]

The new design strategy will provide the possibility for preparing a dynamic sensor by employing the inhibition of C = N isomerization. In this work, the functional probe 4-(1 H-imidazo [4,5-f] [1,10]-phenanthrolin-2-yl) benzaldehyde oxime (compound 4) has been synthesized and such molecule gives rise to blue emission. Due to the incorporation of hypochlorite, the oxime group can be oxidized to the structure of aldehyde. As a result, the molecular motif exhibits sharp emission change from blue to green due to the addition of hypochlorite with enough sensitivity and selectivity (detection limit = 53 nM, linear range 0.5-8.0 µM). It has also been used for monitoring ClO− by employing solution color change and the absorption signal difference could effectively rule out the effects of interference species. To our knowledge, it will be the first case of a highly selective hypochlorite sensor derived from oxime isomerization reaction based on phenanthroline backbone. [ABSTRACT FROM AUTHOR]

Government-sanctioned use of nerve agents (NA) has escalated dramatically in recent years. Oxime reactivators of organophosphate (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) serve as antidotes toward poisoning by OPNAs. The oximes used as therapeutics are quaternary compounds that cannot penetrate the blood–brain barrier (BBB). There remains an urgent need for the development of next generation OPNA therapeutics. We have developed two high-throughput screening (HTS) assays using a fluorogenic NA surrogate, O-ethyl methylphosphonyl O-4-methyl-3-cyano-coumarin (EMP-MeCyC). EMP-MeCyC detoxification and EMP-BChE reactivation screening campaigns of ~155,000 small molecules resulted in the identification of 33 nucleophile candidates, including non-quaternary oximes. Four of the oximes were reactivators of both Sarin- and VX-inhibited BChE and directly detoxified Sarin. One oxime also detoxified VX. The novel reactivators included a non-quaternary pyridine amidoxime, benzamidoxime, benzaldoxime and a piperidyl-ketoxime. The VX-inhibited BChE reactivation reaction rates by these novel molecules were similar to those observed with known bis-quaternary reactivators and faster than mono-quaternary pyridinium oximes. Notably, we discovered the first ketoxime reactivator of OP-ChEs and detoxifier of OPNAs. Preliminary toxicological studies demonstrated that the newly discovered non-quaternary oximes were relatively non-toxic in mice. The discovery of unique non-quaternary oximes opens the door to the design of novel therapeutics and decontamination agents following OPNA exposure. Amitai et al. identified 4 potential small molecule antidotes toward nerve agents poisoning by high-throughput-screening of over 150,000 compounds. Unique non-quaternary oximes represent new potential antidotes for future development as they detoxified nerve agents and also reactivated nerve agent-inhibited butyrylcholinesterase. [ABSTRACT FROM AUTHOR]

Bulky silicalite-1 shows high catalytic activity for vapor phase Beckmann rearrangement of cyclohexanone oxime. However, it often deactivates rapidly and the structure-performance relationship is unclear. Here, a series of well-crystallized silicalite-1 catalysts from three-dimensional micron particles (n < 10) to two-dimensional nanosheets (10 ≤ n ≤ 18) were controllably synthesized using diquaternary ammoniums [CnH2n+1-N+(CH3)2-C6H12-N+(CH3)2-C6H13](Br−)2 (n = 6–18) as the structure directing agent. The influence of morphology of catalysts on active sites distribution and the pore confinement effect on caprolactam selectivity and the catalytic stability were studied by XRD, SEM, TEM, In situ vacuum IR, 29Si MAS NMR and N2 adsorption/desorption isotherms. The silicalite-1 nanosheets with relatively high crystallinity exhibited superior catalytic activity to almost 100% and remarkably high caprolactam selectivity (92%). The catalytic lifetime of silicalite-1 nanosheets could be increased by 28 times in comparison to bulky silicalite-1 zeolite. The external surface area and mesopore volume of the synthesized catalyst dramatically increase with increasing the tail length of surfactant from C6 to C18, leading to high active sites and coke tolerance capacity. It was found the lifetime of the catalysts is almost linearly related to the product of area of silanol nest and volume of mesopore (Asilanol·nest*Vmeso) with correlation coefficient of 0.97, which strongly supports the excellent performance of nanosheets results from the synergetic effect of its high active sites and high coke tolerance capacity. This provides a theoretic guide for designing new catalysts with high catalytic activity. Silicalite-1 nanosheets were controllable synthesized through adjusting alkyl tail length of diquaternary ammoniums, resulting in large mesoporous volume and external surface area, which effectively improve high coke tolerance capacity and active sites of catalysts and exhibit much longer catalytic lifetime and high selectivity. [ABSTRACT FROM AUTHOR]

N-Boc-5-formylpyrazol-4-amines reacted with 1,3-cyclohexanediones in AcOH–1,4-dioxane medium in the presence of pyrrolidine, resulting in the formation of pyrazolo[4,3-b]quinolin-8-one derivatives that were converted into the respective oximes. A reaction of the latter with trifluoromethanesulfonic anhydride under mild conditions was used to synthesize hexahydropyrazolo[3',4':5,6]pyrido[3,2-b]-azepin-4-ium trifluoromethanesulfonates. [ABSTRACT FROM AUTHOR]

Kobusone oxime and hydrazone were synthesized for the first time in yields of 78 and 71%, respectively, via condensation of the sesquiterpene ketone kobusone, which was prepared by oxidation of caryophyllene oxide, with hydroxylamine and hydrazine. Acylation of the caryophyllane oxime and hydrazone produced series of O- and N-derivatives in preparative yields up to 90%. The molecular structures of the acyloximes and acetylhydrazone were established by X-ray crystal structure analyses. [ABSTRACT FROM AUTHOR]

A new method for the preparation of isoxazolylvinyl ketones related to potential cytotoxic agents has been developed. In the first step, the reaction of furfuryl ketones with hydroxylamine hydrochloride affords the corresponding oximes. Further, the oxidative ring opening – ring closure reaction of oximes leads to isoxazoles with an α, β-unsaturated carbonyl motif. The developed procedure is metal-free and does not require expensive starting materials. [ABSTRACT FROM AUTHOR]

The reactions of 2,2-dichlorovinyl ketones with hydroxylamine hydrochloride give the corresponding oximes. The subsequent heterocyclization of the latter under the action of t-BuOK in t-BuOH results in selective formation of 5-chloro-3-alkyl- or 5-chloro-3-aryl-substituted isoxazoles in good yields. [ABSTRACT FROM AUTHOR]

An efficient supported ionic liquid catalyst is designed for condensation reaction of aldehydes and ketones. The Zr-based metal–organic framework (MOF), UiO-66-NH2, was initially functionalized with N,N′-dibutyl imidazolium ionic liquid (UiO-66-NH2-ILBr–), and then urea was attached to the ionic liquid (IL) to form a task-specific IL. Bromide was exchanged with tetrafluoroborate and the catalyst exhibits excellent performance for the synthesis of oximes. The ionic liquid/urea coupling showed a synergistic effect on the efficiency of the reaction. The supported catalyst system was recycled simply by filtration and reused for five times without significant decrease in its activity. The catalyst was characterized with PXRD, FTIR, TGA, XPS, BET, FE-SEM, EDS, elemental mapping and elemental analysis (CHN). MOF/IL/urea catalytic system was used for the synthesis of oximes [ABSTRACT FROM AUTHOR]

In this paper, an approach is proposed for determining the ratio of prototropic annular tautomers of organosilicon 1,2,3-triazoles, which are hardly experimentally determined in solution by NMR technique. The comparison of experimental and calculated (at the CCSD level) NMR chemical shifts allows the predominant tautomer in the equilibrium mixture to be determined. [ABSTRACT FROM AUTHOR]

Treatment of N-propargylated pyrrole aldoxime derivatives with gold-based catalyst unexpectedly resulted in oxime–oxime rearrangement, which led to ketoximes. This type of reorganization has not been previously observed in the literature and represents a new rearrangement called the Balci–Güven rearrangement. Based on the experimental findings, the proposed mechanistic pathway was studied. Density functional theory calculations employing wb97xd, m062x, and m06 hybrid functional methods were used to locate and discuss the energetics of the intermediates and the transition states of this rearrangement. [ABSTRACT FROM AUTHOR]

The oximes of fluorine-containing 6,7-dihydroindazole-4,5-diones and 6,7-dihydrobenzisoxazole-4-5-diones, 5-[3-fluorobenzoyloxy)imino)]-6,6-dimethyl-3-(3-fluorophenyl)-6,7-dihydrobenz[d]]isoxazol-4(5H)-one, and 5,5-dimethyl-7-phenyl-9-(4-fluorophenyl)-3,5,6,7-tetrahydro-2H-pyrazolo[4,3-f]quinoxaline were synthesized. The cytotoxic activity of these compounds against cell lines MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) was determined. The fluorine-containing 6,7-dihydroindazolone derivatives synthesized here included substances with marked antiproliferative activity, the mechanism of which may be linked with induction of apoptosis due to impairment of the regular cell cycle, i.e., delayed of tumor cells in the G2/M phase. [ABSTRACT FROM AUTHOR]

There is an urgent need for the design and development of new and safer drugs for the treatment of HIV infection, active against the currently resistant viral strains by development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of pregnenolone analogues, 3-((aryl)-1-(5-pregnen-3β-ol-17-yl)prop-2-en-1-ones, were synthesized. Further, treatment of 3-((4-bromo-, 4-trifluoromethyl, or 4-methylphenyl)-1-(preg-5-en-3β-ol-17-yl)prop-2-en-1-ones with thiosemicarbazide in ethanolic KOH or hydrazine hydrate in HOAc gave 5-(4-bromo-, 4-trifluoromethyl, or 4-methylphenyl)-3-(preg-5-en-3β-ol-17-yl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides and 1-O-acetyl-(5-(4-bromophenyl)-3-(preg-5-en-3β-ol-17-yl)-4,5-dihydro-1H-pyrazoline, respectively. Analogously, treatment of 3-((4-bromophenyl)-1-(preg-5-en-3β-ol-17-yl)prop-2-en-1-one with hydroxylamine afforded the Z/E isomers of 3-(4-bromophenyl)-1-(preg-5-en-3β-ol-17-yl)prop-2-en-1-one oxime. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 3-(thiophene-2-yl)-1-(preg-5-en-3β-ol-17-yl)prop-2-en-1-one and 1-O-acetyl-(5-(4-bromophenyl)-3-(preg-5-en-3β-ol-17-yl)-4,5-dihydro-1H-pyrazoline were the most active in inhibiting HIV-1 and HIV-2 with IC50 = 60.5 μM (SI > 2, against HIV-2 and SI < I against HIV-1), and > 0.29 μM (SI < I), respectively, suggesting to be new leads in the development of antiviral agents. QSAR of 3-((aryl)-1-(5-pregnen-3β-ol-17-yl)prop-2-en-1-ones and 5-(substituted phenyl)-3-(5-preg-5-3β-ol-17-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamides has been studied. The conformational analysis of 5-(4-trifluoromethylphenyl)-3-(preg-5-en-3β-ol-17-yl)-4,5-dihydro-1H-pyrazoline-1-carbothioamide and 1-O-acetyl-(5-(4-bromophenyl)-3-(preg-5-en-3β-ol-17-yl)-4,5-dihydro-1H-pyrazoline as well as the molecular docking study of the latter compound have been investigated. [ABSTRACT FROM AUTHOR]

A methodology for synthesizing amino-acid derivatives of pyranocoumarins in three steps using pyranocoumarin oximes as starting compounds was developed. A series of pyranocoumarins containing the amino acids glycine, alanine, phenylalanine, methionine, leucine, and β-alanine in their structures could be prepared using the activated ester method. [ABSTRACT FROM AUTHOR]

Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more than six decades. Established oximes, i.e. pralidoxime, obidoxime, TMB-4, HI-6 and MMB-4, are of insufficient effectiveness in some poisonings and often cover only a limited spectrum of the different nerve agents and pesticides. Moreover, the value of oximes in human OP pesticide poisoning is still disputed. Long-lasting research efforts resulted in the preparation of countless experimental oximes, and more recently non-oxime reactivators, intended to replace or supplement the established and licensed oximes. The progress of this development is slow and none of the novel compounds appears to be suitable for transfer into advanced development or into clinical use. This situation calls for a critical analysis of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators. Requirements for a straightforward identification of superior reactivators and their development to licensed drugs need to be addressed as well as options for interim solutions as a chance to improve the therapy of OP poisoning in a foreseeable time frame. [ABSTRACT FROM AUTHOR]

Structures were established for the products of the reactions of 2,2-di(4-nitrophenyl)-1-chloroethene and 2,2-di(4-nitrophenyl)-1,1-dichloroethene with sodium nitrite and the ratio of these products was found using chemical balance, high-performance liquid chromatography, and IR spectroscopy data. The reaction of 2,2-di-(4-dinitrophenyl)-1-chloroethene with nitrite ion in dimethylformamide gives 50% 4,4'-dinitrobenzophenone, 30% 4,4'-dinitrobenzophenone oxime, and 20% 4,4'-dinitrobenzanilide. The products of the reaction of 2,2-di(4-nitrophenyl)-1,1-dichloroethene with NaNO2 in DMF gives 95–97% 4,4'-dinitrobenzophenone and 2.5–3.0% 4,4'-dinitrobenzophenone oxime. [ABSTRACT FROM AUTHOR]