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Journal of Agricultural and Food... Nov 2022The accumulation of residual active herbicides in the environment can cause a series of problems. It is thus meaningful to explore a photoresponsive herbicide, whose...
The accumulation of residual active herbicides in the environment can cause a series of problems. It is thus meaningful to explore a photoresponsive herbicide, whose activity can be weakened under the action of light to reduce the negative effect. To this purpose, a series of ()/()-verbenone oxime ethers were designed, synthesized, and characterized. Oxime ether groups were adopted as the trigger switches. The preliminary screening for herbicidal activity showed that some of them exhibited better or comparable effects than that of the commercial herbicide flumioxazin against and . Meanwhile, five pairs of the target compounds with significantly different herbicidal effects between - and -forms were further investigated for their reversible isomerization reaction and the accompanying variation of herbicidal activity. As a result, the maximum conversion rates were around 50%, and the herbicidal effect of the resulting mixture of - and -isomers decreased outstandingly. The phototransformation mechanism of a pair of isomers ()- and ()- was preliminarily explored. Besides, a reasonable and effective 3D-quantitative structure-activity relationship model ( = 0.984 and = 0.571) was established and the binding mode was also investigated by molecular docking.
Topics: Herbicides; Oximes; Molecular Docking Simulation; Ethers
PubMed: 36278958
DOI: 10.1021/acs.jafc.2c05766 -
Biomacromolecules Apr 2023A series of four oxime-linked octavalent sialic acid and oligosialic acid poly(ether amidoamine) glycodendrimers were synthesized. In the attachment of the sialic acids...
A series of four oxime-linked octavalent sialic acid and oligosialic acid poly(ether amidoamine) glycodendrimers were synthesized. In the attachment of the sialic acids to the dendrimer core, chemoselective oxime bonds were formed between the unprotected sugars (sialic acid or α-2,8-linked di- through tetra-sialic acids) and the aminooxy-terminated dendrimer core in a microwave-mediated reaction, resulting in good to excellent yields (58-100%) of the fully functionalized octavalent glycodendrimers. Next, using a combination of 1D and 2D nuclear magnetic resonance and working from the inside outward, we employed a systematic method to assign the proton and carbon signals starting with the smallest linkers and dendrimer cores and moving gradually up to the completed octavalent glycodendrimers. Through this approach, the assignment of the protons and carbons was possible, including the - and -isomers related to the oxime dendrimer to sugar connections and relative quantities of each. These glycodendrimers were designed as broad-spectrum inhibitors of viral pathogens.
Topics: N-Acetylneuraminic Acid; Oximes; Dendrimers; Magnetic Resonance Spectroscopy; Sialic Acids
PubMed: 36989087
DOI: 10.1021/acs.biomac.3c00105 -
Bioorganic & Medicinal Chemistry Feb 2021A series of novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether moieties were designed and synthesized. Their anticancer activities were...
A series of novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether moieties were designed and synthesized. Their anticancer activities were evaluated by MTT assay, the results showed that most compounds exhibited extremely inhibitory effects against hepatoma SMMC-7721 cells. In particular, compounds Q2 and Q8 displayed the more potent inhibitory activity with IC values of 0.64 and 0.63 μM, which were better than that of gemcitabine (1.40 μM). Further mechanism studies indicated that compounds Q2, Q8, Q13 and Q19 could control the migration of SMMC-7721 cells effectively, and inhibit the proliferation of cancer cells by inhibiting the DNA replication. Western-blot results showed that compounds Q2 and Q8 induced irreversible apoptosis of SMMC-7721 cells by regulating the expression level of apoptose-related proteins. Those studies demonstrated that the penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments merited further research as potential anticancer agents.
Topics: Alkadienes; Antineoplastic Agents; Apoptosis; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Oximes; Quinazolines; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 33444848
DOI: 10.1016/j.bmc.2021.115999 -
Toxicology Jul 2019The misuse of organophosphate compounds still represents a current threat worldwide. Treatment of poisoning with organophosphates (OPs) remains unsatisfactorily resolved... (Review)
Review
The misuse of organophosphate compounds still represents a current threat worldwide. Treatment of poisoning with organophosphates (OPs) remains unsatisfactorily resolved despite the extensive investment in research in academia. There are no universal, effective and centrally-active acetylcholinesterase (AChE) reactivators to countermeasure OP intoxication. One major obstacle is to overcome the blood-brain barrier (BBB). The central compartment is readily accessible by the OPs which are lipophilic bullets that can easily cross the BBB, whereas first-line therapeutics, namely oxime-based AChE reactivators and atropine, do not cross or do so rather slowly. The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. The aim of this article is to review the methods for targeting the brain by oxime reactivators that have been developed so far. Approaches using prodrugs, lipophilicity enhancement, or sugar-based oximes have been rather unsuccessful. However, other strategies have been more promising, such as the use of nanoparticles or co-administration of the reactivator with efflux transporter inhibitors. Encouraging results have also been associated with intranasal delivery, but research in this field is still at the beginning. Further research of auspicious approaches is inevitable.
Topics: Animals; Biological Transport; Brain; Cholinesterase Inhibitors; Cholinesterase Reactivators; Humans; Organophosphate Poisoning; Oximes
PubMed: 31112674
DOI: 10.1016/j.tox.2019.05.006 -
Nuclear Medicine Review. Central &... 2023A challenge for modern medicine is the development of clinical protocols for precise diagnosis and therapy. This study aimed to propose a simple method for modification...
BACKGROUND
A challenge for modern medicine is the development of clinical protocols for precise diagnosis and therapy. This study aimed to propose a simple method for modification of 2-[18F]FDG used routinely in hospitals in a way, appropriate for patients' personalized radiopharmaceuticals approach.
MATERIAL AND METHODS
For the purposes of the presented study chemo selective method for indirect radiofluorination was applauded to custom synthesized aminooxy- and hydrazine-functionalized tetrazines for 18F-glycolation via oxime or hydrazone formation. 2-[18F]FDG produced with medical baby cyclotron in Nuclear Medicine Clinic at the University Hospital St. Marina-Varna, was used. Thin layer chromatography (TLC) and radio TLC were used to follow the progress of synthesis and to determine radio chemical yield (RCY).
RESULTS
The 2-[18F]FDG was modified with two bifunctional tetrazines aminooxy-acetic acid-6-(2-aminooxy-acetoxy)-[1,2,4,5] tetrazin-3-yl ester (Tz1) and {3-[4-(6-phenyl-[1,2,4,5]tetrazin-3-yl)-phenoxy]-propyl}-hydrazine (Tz2) via oxime and hydrazone formation. The radiolabeling was carried out as one-pot reaction with following parameters: temperature 70-75°C; catalyst p- diaminobenzene (Cat.); pH = 4.2; time 30 minutes; RCY = 70-99%. The radiolabeled tetrazines are appropriate for further bioorthogonal (pretargeting) strategy by click reactions with trans-cyclooctene conjugated bioactive molecules. The methodology is applicable to standard clinical conditions.
Topics: Humans; Fluorodeoxyglucose F18; Radiopharmaceuticals; Glucose; Oximes
PubMed: 37786914
DOI: 10.5603/nmr.93869 -
British Journal of Clinical Pharmacology Dec 2022Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was...
Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was developed in the 1950s and was soon noted to benefit patients occupationally poisoned with the highly potent OP insecticide parathion. Routine use of pralidoxime and other oximes such as obidoxime then became widely recommended. However, nearly all severe cases of OP poisoning now result from self-poisoning with large volumes of less potent (WHO hazard class Ib and II) insecticides and co-formulated solvents. Unfortunately, oxime clinical trials have never shown benefit from their use for these patients, and some have shown that pralidoxime may be associated with harm, including increased mortality. Oximes should not be used routinely for the care of OP insecticide-poisoned patients until translational and clinical studies have identified a safe and effective oxime regimen and identified the patients who benefit.
Topics: Humans; Insecticides; Oximes; Acetylcholinesterase; Organophosphorus Compounds; Organophosphate Poisoning; Cholinesterase Inhibitors; Poisoning
PubMed: 34989015
DOI: 10.1111/bcp.15217 -
Basic & Clinical Pharmacology &... Apr 2020The inhibition of acetylcholinesterase (AChE) is a common outcome caused by organophosphorus (OPs) intoxication. Although inconsistent, the standard treatment consists... (Comparative Study)
Comparative Study
The inhibition of acetylcholinesterase (AChE) is a common outcome caused by organophosphorus (OPs) intoxication. Although inconsistent, the standard treatment consists of a muscarinic receptor antagonist (atropine) and AChE-reactivating molecules such as oximes. This study proposes to test unpublished compounds which contain the moieties of isatin and/or oxime have protective effects against the toxicity induced by malathion in two animal models: Artemia salina and Rattus norvegicus (Wistar rats). The lethality was assessed in A salina, and the calculated LD to (3Z)-5-chloro-3-(hydroxyimino) indolin-2-one oxime (Cℓ-HIN) and 2-(5-chloro-2-oxoindolin-3-ylidene)-hydrazinecarbothioamide (Cℓ-OXHS) was higher than 1000 µM while to 3-(phenylhydrazono) butan-2-one oxime (PHBO) was 38 µM. Our screening showed that Cℓ-HIN seems to be the most promising molecule, with low toxicity to A salina, protection against mortality (with or without atropine) and AChE inhibition induced by malathion. Similarly, the oral administration of 300 mg/kg of Cℓ-HIN induced low or no toxicity in rats. The plasma butyrylcholinesterase (BChE) and cortical AChE activities were reactivated by Cℓ-HIN (50 mg/kg, p.o.) in rats exposed to malathion (250 mg/kg, i.p). No difference was observed in paraoxonase-1 (PON-1) activity among groups treated. In conclusion, Cℓ-HIN restored the cholinesterase activities inhibited by malathion in A salina and rats with low toxicity in both. Thus, the data provide evidence that Cℓ-HIN, a compound that combines isatin and oxime functional groups, is safe and has important properties to reactivate the cholinesterases inhibited by malathion. In addition, we demonstrate the importance of a preliminary assessment in an alternative model in order to reduce the use of mammalians in drug discovery.
Topics: Animals; Artemia; Cholinesterase Inhibitors; Cholinesterase Reactivators; Disease Models, Animal; Drug Discovery; Female; Insecticides; Isatin; Lethal Dose 50; Malathion; Male; Oximes; Rats; Rats, Wistar
PubMed: 31694074
DOI: 10.1111/bcpt.13359 -
Journal of Materials Chemistry. B Oct 2023Far-red BODIPY-based oxime esters for photo-uncaging were designed to release molecules of interest with carboxylic acids. The low power red LED light breaks the N-O...
Far-red BODIPY-based oxime esters for photo-uncaging were designed to release molecules of interest with carboxylic acids. The low power red LED light breaks the N-O oxime ester bond and frees the caged molecules. We studied the mechanism and kinetics of the uncaging procedure using a H NMR spectrometer. Moreover, the drug delivery strategy to release valproic acid (VPA) on demand was tested using this far-red BODIPY photo-uncaging strategy to induce apoptosis in tumor cells.
Topics: Esters; Oximes; Light; Boron Compounds
PubMed: 37850246
DOI: 10.1039/d3tb01867a -
Journal of Materials Chemistry. B Jul 2022Oxime formation is a convenient one-step method for ligating reducing sugars to surfaces, producing a mixture of closed ring α- and β-anomers along with open-chain ()-...
Oxime formation is a convenient one-step method for ligating reducing sugars to surfaces, producing a mixture of closed ring α- and β-anomers along with open-chain ()- and ()-isomers. Here we show that despite existing as a mixture of isomers, -acetylglucosamine (GlcNAc) oximes can still be substrates for β(1,4)-galactosyltransferase (β4GalT1). β4GalT1 catalysed the galactosylation of GlcNAc oximes by a galactose donor (UDP-Gal) both in solution and on the surface of liposomes, with conversions up to 60% in solution and 15-20% at the liposome surface. It is proposed that the β-anomer is consumed preferentially but long reaction times allow this isomer to be replenished by equilibration from the remaining isomers. Adding further enzymes gave more complex oligosaccharides, with a combination of α-1,3-fucosyltransferase, β4GalT1 and the corresponding sugar donors providing Lewis X coated liposomes. However, sialylation using trans-sialidase and sialyllactose provided only very small amounts of sialyl Lewis X (sLe) capped lipid. These observations show that combining oxime formation with enzymatic elaboration will be a useful method for the high-throughput surface modification of drug delivery vehicles, such as liposomes, with cell-targeting oligosaccharides.
Topics: Acetylglucosamine; Glycoconjugates; Liposomes; Oligosaccharides; Oximes
PubMed: 35723603
DOI: 10.1039/d2tb00714b -
The Journal of Organic Chemistry Feb 2023Prenyl functionalities have been widely discovered in natural products, nucleic acids, and proteins with significant biological roles in both healthy and diseased cells....
Prenyl functionalities have been widely discovered in natural products, nucleic acids, and proteins with significant biological roles in both healthy and diseased cells. In this work, we develop a series of new nitroso-based probes for the labeling, enrichment, and regulation of prenylated RAS protein, which is highly associated with ∼20% of human cancers and used to be regarded as an "undruggable" target via a sequential ene-ligation and oxime condensation (SELOC) process. We found that these nitroso species can rapidly react with prenyl-containing molecules through ene-ligation and install a molecular tag for functional applications under physiological conditions. We first investigated this ligation process on two peptide models and demonstrated its labeling efficiency on various proteins such as myoglobin, lysozyme, RNase A, BSA, and HSP40. We further coupled this reactive platform with proteolysis-targeting chimera technology targeting to increase its efficiency and accuracy, as well as to expand its application range. Using the prenylated RAS protein as the model, we demonstrated that RAS could be efficiently decorated with our nitroso probes, which further condensate with oxime and rapidly react with a pomalidomide-containing hydroxylamine probe for protein degradation. As a result, the RAS protein in both HeLa and A549 cell lines has been determined to be efficiently degraded both in vitro and in vivo. This is the first case targeting post-translational modification other than ligand-protein interaction to degrade and regulate RAS proteins. We envision that our SELOC strategy will have great potential in studying the fundamental structures and functions of prenylated biomolecules and developing new drugs based on these unique cellular pathways.
Topics: Humans; Oximes; ras Proteins; Proteins; HeLa Cells; Neoplasms
PubMed: 36691112
DOI: 10.1021/acs.joc.2c02922