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Molecules (Basel, Switzerland) Mar 2018Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks... (Review)
Review
Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks based on nucleosides and sugars is in high demand for the generation of novel oligonucleotide mimics and glycoconjugates for biomedical applications. Recently, aminooxyl-functionalized compounds have attracted increasing research interest because of their easy derivatization through oxime ligation or -oxyamide formation reactions. Various biological applications have been reported for -amino carbohydrate- and nucleoside-derived compounds. Here, we report our efforts in the design and synthesis of glyco-, glycosyl, nucleoside- and nucleo-aminooxy acid derivatives from readily available sugars and amino acids, and their use for the generation of -oxyamide-linked oligosaccharides, glycopeptides, glycolipids, oligonucleosides and nucleopeptides as novel glycoconjugates or oligonucleotide mimics. Delicate and key points in the synthesis will be emphasized.
Topics: Amino Sugars; Molecular Structure; Nucleosides; Oximes
PubMed: 29534554
DOI: 10.3390/molecules23030641 -
Journal of the American Chemical Society Nov 2019Bioorthogonal reactions are valuable tools for the selective labeling and imaging of natural products and proteins. Here, we present the reaction between isonitriles and...
Bioorthogonal reactions are valuable tools for the selective labeling and imaging of natural products and proteins. Here, we present the reaction between isonitriles and chlorooximes as a ligation that proceeds quickly ( ≈ 1 M s) and with high chemoselectivity in an aqueous environment. Imaging of metabolically labeled cell surface glycans underlined the tolerance of the ligation to common functional groups in cellular systems. Live-cell dual-labeling experiments revealed that the isonitrile-chlorooxime ligation is orthogonal to the strain-promoted azide-alkyne cycloaddition.
Topics: Animals; CHO Cells; Cricetulus; Kinetics; Nitriles; Oximes; Polysaccharides
PubMed: 31710811
DOI: 10.1021/jacs.9b07632 -
ChemMedChem Sep 2021Several naturally occurring cyclopentenones, such as palmenones and nigrosporiones, exhibit antimicrobial activity. Herein we describe the antimicrobial activity of...
Several naturally occurring cyclopentenones, such as palmenones and nigrosporiones, exhibit antimicrobial activity. Herein we describe the antimicrobial activity of cyclopentenones and derivatives that can be easily accessed from biomass derivatives furfural and 5-hydroxymethylfurfural. Upon screening a range of functionalized trans-diamino-cyclopentenones (DCPs) and δ-lactone-fused cyclopentenones (LCPs), an oxime ether derivative of DCP was identified that exhibited remarkable antimicrobial activity against Gram-positive bacteria, including resistant strains such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE) strains.
Topics: Anti-Bacterial Agents; Cyclopentanes; Dose-Response Relationship, Drug; Enterococcus faecalis; Ether; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Oximes; Structure-Activity Relationship; Vancomycin Resistance
PubMed: 34115919
DOI: 10.1002/cmdc.202100369 -
Annals of the New York Academy of... Jun 2016The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE),... (Review)
Review
The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure.
Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Enzyme Activation; Models, Animal; Organophosphorus Compounds; Oximes; Zebrafish
PubMed: 27123828
DOI: 10.1111/nyas.13051 -
Molecules (Basel, Switzerland) May 2021The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal...
The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.
Topics: Cell Cycle; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA; Estrogen Receptor alpha; Estrogens; Estrone; Fluorouracil; Humans; Inhibitory Concentration 50; Molecular Docking Simulation; Oximes
PubMed: 34064380
DOI: 10.3390/molecules26092687 -
Toxicology May 2023Despite the large number of odoriferous compounds available, new ones with interesting olfactory characteristics are desired due to their potentially high commercial...
Despite the large number of odoriferous compounds available, new ones with interesting olfactory characteristics are desired due to their potentially high commercial value. Here, we report for the first time mutagenic, genotoxic, and cytotoxic effects, and antimicrobial properties of low-molecular fragrant oxime ethers, and we compare their properties with corresponding oximes and carbonyl compounds. 24 aldehydes, ketones, oximes, and oxime ethers were evaluated for mutagenic and cytotoxic effects in Ames (using Salmonella typhimurium strains TA 98 with genotype hisD3052, rfa, uvrB, pKM101, and TA100 with genotype hisG46, rfa, uvrB, pKM101, concentration range: 0.0781-40 mg/mL) and MTS (using HEK293T cell line concentration of tested substances: 0.025 mM) assays. Antimicrobial evaluation was carried out against Bacillus cereus (ATCC 10876), Staphylococcus aureus (ATCC 6538), Enterococcus hirae (ATCC 10541), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 10536), Legionella pneumophila (ATCC 33152); Candida albicans (ATCC 10231) and Aspergillus brasiliensis (ATCC 16404) with concentration range of tested substances 9.375 - 2.400 mg/mL. Furthermore, 5 representatives of carbonyl compounds, oximes, and an oxime ether (stemone, buccoxime, citral, citral oxime, and propiophenone oxime O-ethyl ether) were evaluated for genotoxic properties in SOS-Chromotest (concentration range: 7.8·10 - 5·10 mg/mL). All of the tested compounds did not exhibit mutagenic, genotoxic, or cytotoxic effects. Oximes and oxime ethers showed relevant antimicrobial activity against pathogenic species (P. aeruginosa, S. aureus, E.coli, L. pneumophila, A. brasiliensis, C. albicans) in the MIC range 0.075 - 2.400 mg/mL compared to the common preservative methylparaben with the MIC range 0.400-3.600 mg/mL. Our study shows that oxime ethers have the potential to be used as fragrant agents in functional products.
Topics: Humans; Antifungal Agents; Ethers; Mutagens; Oximes; Ketones; Aldehydes; Odorants; Staphylococcus aureus; HEK293 Cells; Microbial Sensitivity Tests; Anti-Infective Agents; DNA Damage
PubMed: 37059348
DOI: 10.1016/j.tox.2023.153510 -
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