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Molecules (Basel, Switzerland) Jun 2023Oxime ethers are a class of compounds containing the >C=N-O-R moiety. The presence of this moiety affects the biological activity of the compounds. In this review, the... (Review)
Review
Oxime ethers are a class of compounds containing the >C=N-O-R moiety. The presence of this moiety affects the biological activity of the compounds. In this review, the structures of oxime ethers with specific biological activity have been collected and presented, and bactericidal, fungicidal, antidepressant, anticancer and herbicidal activities, among others, are described. The review includes both those substances that are currently used as drugs (e.g., fluvoxamine, mayzent, ridogrel, oxiconazole), as well as non-drug structures for which various biological activity studies have been conducted. To the best of our knowledge, this is the first review of the biological activity of compounds containing such a moiety. The authors hope that this review will inspire scientists to take a greater interest in this group of compounds, as it constitutes an interesting research area.
Topics: Ethers; Structure-Activity Relationship; Oximes; Fungicides, Industrial; Anti-Bacterial Agents; Anesthetics, General
PubMed: 37446703
DOI: 10.3390/molecules28135041 -
Archives of Toxicology Mar 2014Oxime-type acetylcholinesterase reactivators (oxime-AChER) are used as an adjunct in the treatment for organophosphorus anticholinesterase poisoning. Because of the... (Review)
Review
Oxime-type acetylcholinesterase reactivators (oxime-AChER) are used as an adjunct in the treatment for organophosphorus anticholinesterase poisoning. Because of the widespread usage and exposure of organophosphorus compounds (OPCs), its poisoning and fatalities is obvious in pregnant women, embryos and fetuses. OPCs irreversibly inhibit acetylcholinesterase (AChE) at nerve synapses. Furthermore, the role of AChE other than neurotransmission termination has been defined in the literature. The growing evidences show that cholinergic mechanisms are involved during growth and development of other organ systems. In contrary to the fact, the data on the use of oxime-AChER in OPC poisoning in pregnancy are scanty. The present review aimed to comprehend the status of oximes in pregnancy in lieu of the published literature. A thorough literature search was performed in January 2013, using ten popular search engines including Medline/PubMed, Google scholar, etc., using nine standard keywords. The search period was set from 1966 to present. The search did not reveal substantial data. No considerable studies were retrieved which could really demonstrate either the beneficial, harmful or even null effect of oxime-AChER usage in pregnancy. Only eighteen relevant articles were obtained for a period of about 47 years. In the literature, there is no report available to demonstrate the risk of using oxime-AChER in pregnancy for the treatment of OPC poisoning. The study reveals that the use of oxime-AChER in pregnancy is largely un-addressed, inconclusive and based on speculation albeit the incidences of OPC poisoning are quite prevalent. Well-designed studies are warranted for a tangible conclusion.
Topics: Antidotes; Cholinesterase Reactivators; Female; Humans; Organophosphate Poisoning; Oximes; Pralidoxime Compounds; Pregnancy
PubMed: 24258240
DOI: 10.1007/s00204-013-1160-z -
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 -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2014There is a growing need for biocompatible click reactions in order to prepare multifunctional conjugates, which are valuable molecules for innovative biomedical... (Review)
Review
There is a growing need for biocompatible click reactions in order to prepare multifunctional conjugates, which are valuable molecules for innovative biomedical applications. In this context, we review the recent advances in the implementation of oxime ligation for the synthesis of multivalent or multicomponent systems. The value of these products is emphasized by their use in cell targeting, imaging, synthetic vaccines, and surface modifications.
Topics: Animals; Click Chemistry; Leptin; Nanoparticles; Neoplasms; Neovascularization, Pathologic; Oxidation-Reduction; Oximes; Surface Properties; Vaccines, Synthetic
PubMed: 24302514
DOI: 10.1002/chem.201302426 -
International Journal of Molecular... Nov 2023The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse... (Review)
Review
The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure-activity relationship studies. An extensive literature search was conducted across three databases, including PubMed, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure-activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anticancer potential of this group of molecules across diverse molecular scaffolds.
Topics: Ether; Oximes; Ethers; Structure-Activity Relationship; Ethyl Ethers
PubMed: 38069175
DOI: 10.3390/ijms242316854 -
Organic Letters Apr 2023The biocompatible synthesis of constrained peptides is challenging. Oxime ligation is a bioorthogonal technique frequently used for protein bioconjugation. We report a...
The biocompatible synthesis of constrained peptides is challenging. Oxime ligation is a bioorthogonal technique frequently used for protein bioconjugation. We report a straightforward method to install N-terminal ketones and aminooxy side chains during standard solid-phase peptide synthesis. Cyclization occurs spontaneously after acidic cleavage or in aqueous buffer. We demonstrate the facile synthesis of protease inhibitors with varying conformational constraint. The most constrained peptide displayed an activity 2 orders of magnitude higher than its linear analog.
Topics: Oximes; Peptides; Proteins; Solid-Phase Synthesis Techniques; Cyclization; Peptides, Cyclic
PubMed: 37053571
DOI: 10.1021/acs.orglett.3c00695 -
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 -
Organic Letters Jun 2015The gold-catalyzed reaction of pyrrole and indole oximes having a propargyl group attached to the nitrogen atom was studied. The selective 6-endo-dig mode of cyclization...
The gold-catalyzed reaction of pyrrole and indole oximes having a propargyl group attached to the nitrogen atom was studied. The selective 6-endo-dig mode of cyclization was observed for the terminal alkynes giving rise to the formation of pyrazine N-oxides in the presence of a gold catalyst. However, the reaction with substituted alkyne transferred the oxime functionality intramolecularly from one carbon atom to another via the 7-endo-dig cyclization process. This transformation is unprecedented in the literature and is named an oxime-oxime rearrangement.
Topics: Catalysis; Gold; Indoles; Molecular Structure; Oximes; Pyrroles
PubMed: 25992473
DOI: 10.1021/acs.orglett.5b01041 -
Organic & Biomolecular Chemistry Jun 2017Carbohydrate microarrays represent powerful tools to study and detect carbohydrate-binding proteins, pathogens or cells. In this paper, we report two original...
Carbohydrate microarrays represent powerful tools to study and detect carbohydrate-binding proteins, pathogens or cells. In this paper, we report two original oxime-based methods to prepare surfaces displaying well-defined structures and valency in a given microspot with improved recognition potency with lectins. In a first "direct" approach, fully synthetic aminooxylated glycoclusters have been coated onto aldehyde-activated SiO (silicium substrate doped with 50 nm thermal oxide layer). To improve the preparation of the microarray in terms of rapidity and simplicity and to provide addressable surfaces on which sugars can be linked chemoselectively as clusters at defined plots, a second "indirect" strategy has been developed using successive oxime ligation steps. In both cases, binding assays with labelled lectins have revealed more potent and selective interaction due to the clustered presentation of sugars. The observed differences of interaction have been confirmed in solution by ITC.
Topics: Carbohydrates; Microarray Analysis; Molecular Conformation; Oximes
PubMed: 28604904
DOI: 10.1039/c7ob00889a -
Photochemistry and Photobiology Mar 2022Despite its promising role in the active control of biological functions by light, photocaging remains untested in acetylcholinesterase (AChE), a key enzyme in the...
Despite its promising role in the active control of biological functions by light, photocaging remains untested in acetylcholinesterase (AChE), a key enzyme in the cholinergic family. Here, we describe synthesis, photochemical properties and biochemical activities of two caged oxime compounds applied in the photocontrolled reactivation of the AChE inactivated by reactive organophosphate. Each of these consists of a photocleavable coumarin cage tethered to a known oxime reactivator for AChE that belongs in an either 2-(hydroxyimino)acetamide or pyridiniumaldoxime class. Of these, the first caged compound was able to successfully go through oxime uncaging upon irradiation at long-wavelength ultraviolet light (365 nm) or visible light (420 nm). It was further evaluated in AChE assays in vitro under variable light conditions to define its activity in the photocontrolled reactivation of paraoxon-inactivated AChE. This assay result showed its lack of activity in the dark but its induction of activity under light conditions only. In summary, this article reports a first class of light-activatable modulators for AChE and it offers assay methods and novel insights that help to achieve an effective design of caged compounds in the enzyme control.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Cholinesterase Reactivators; Oximes; Paraoxon
PubMed: 34558680
DOI: 10.1111/php.13530