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Topics in Current Chemistry (Cham) May 2023Oxime esters as the applicable building blocks, internal oxidizing agents, and directing groups in the synthesis of -, S-, and O-containing heterocycle scaffolds have... (Review)
Review
Oxime esters as the applicable building blocks, internal oxidizing agents, and directing groups in the synthesis of -, S-, and O-containing heterocycle scaffolds have gained great attention in the last decade. This review provides an overview of recent advances in the cyclization of oxime esters with various functional group reagents under transition metal and transition metal-free catalyzed conditions. Moreover, the mechanistic aspects of these protocols are explained in detail.
Topics: Molecular Structure; Oximes; Esters; Catalysis; Transition Elements
PubMed: 37202650
DOI: 10.1007/s41061-023-00431-y -
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 -
International Journal of Molecular... May 2019Naringenin is one of the most abundant dietary flavonoids exerting several beneficial biological activities. Synthetic modification of naringenin is of continuous...
Naringenin is one of the most abundant dietary flavonoids exerting several beneficial biological activities. Synthetic modification of naringenin is of continuous interest. During this study our aim was to synthesize a compound library of oxime and oxime ether derivatives of naringenin, and to investigate their biological activities. Two oximes and five oxime ether derivatives were prepared; their structure has been elucidated by NMR and high-resolution mass spectroscopy. The antiproliferative activity of the prepared compounds was evaluated by MTT assay against human leukemia (HL-60) and gynecological cancer cell lines isolated from cervical (HeLa, Siha) and breast (MCF-7, MDA-MB-231) cancers. -butyl oxime ether derivative exerted the most potent cell growth inhibitory activity. Moreover, cell cycle analysis suggested that this derivative caused a significant increase in the hypodiploid (subG1) phase and induced apoptosis in Hela and Siha cells, and induced cell cycle arrest at G2/M phase in MCF-7 cells. The proapoptotic potential of the selected compound was confirmed by the activation of caspase-3. Antioxidant activities of the prepared molecules were also evaluated with xanthine oxidase, DPPH and ORAC assays, and the methyl substituted oxime ether exerted the most promising activity.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Flavanones; HeLa Cells; Humans; MCF-7 Cells; Neoplasms; Oximes; Structure-Activity Relationship
PubMed: 31052551
DOI: 10.3390/ijms20092184 -
Chemical Communications (Cambridge,... Nov 2022Herein, the Rh(III)-catalysed C(sp)-H bond amidation of 8-methylquinolines using -hydroxyphthalimides as the amidation source is explored. Diversely substituted...
Herein, the Rh(III)-catalysed C(sp)-H bond amidation of 8-methylquinolines using -hydroxyphthalimides as the amidation source is explored. Diversely substituted 8-methylquinolines were well tolerated and furnished the amidated products in excellent yields with high regioselectivity. The developed reaction conditions were also applied successfully for the secondary C(sp)-H amidation of 8-ethylquinolines. Besides that, the reaction is also applicable for the gram-scale synthesis of the amidated product. In addition, the late-stage amidation of santonin oxime as well as carvone oxime and the diversification of the amidated product was also carried out to illustrate the relevance of the developed methodology. Mechanistic studies revealed that the current reaction proceeds through a five-membered rhodacycle intermediate and does not involve the radical pathway.
Topics: Rhodium; Quinolines; Oximes
PubMed: 36349998
DOI: 10.1039/d2cc04772a -
Biomolecules May 2021Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have... (Review)
Review
Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide. This review is focused on oximes as kinase inhibitors with anticancer and anti-inflammatory activities. Oximes with non-kinase targets or mechanisms of anti-inflammatory activity are also discussed.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Enzyme Inhibitors; Humans; Neoplasm Proteins; Neoplasms; Oximes; Phosphotransferases
PubMed: 34067242
DOI: 10.3390/biom11060777 -
Organic Letters May 2020This study involves the total synthesis of casuarinin, a naturally occurring ellagitannin, in which an open-chain glucose is esterified with two ()-hexahydroxydiphenoyl...
This study involves the total synthesis of casuarinin, a naturally occurring ellagitannin, in which an open-chain glucose is esterified with two ()-hexahydroxydiphenoyl (HHDP) groups. One HHDP group incorporates a C-glycosidic bond between its benzene ring and the glucose moiety, which was constructed with complete stereoselectivity using a benzyl oxime group that opened the glucopyranose ring and acted as a scaffold for C-glycoside production. This total synthesis enables future structure-activity relationship studies of this compound.
Topics: Glycosides; Glycosylation; Hydrolyzable Tannins; Oximes; Stereoisomerism
PubMed: 32275157
DOI: 10.1021/acs.orglett.0c00876 -
Molecular Plant Jan 2018Oximes (RRC=NOH) are nitrogen-containing chemical constituents that are formed in species representing all kingdoms of life. In plants, oximes are positioned at... (Review)
Review
Oximes (RRC=NOH) are nitrogen-containing chemical constituents that are formed in species representing all kingdoms of life. In plants, oximes are positioned at important metabolic bifurcation points between general and specialized metabolism. The majority of plant oximes are amino acid-derived metabolites formed by the action of a cytochrome P450 from the CYP79 family. Auxin, cyanogenic glucosides, glucosinolates, and a number of other bioactive specialized metabolites including volatiles are produced from oximes. Oximes with the E configuration have high biological activity compared with Z-oximes. Oximes or their derivatives have been demonstrated or proposed to play roles in growth regulation, plant defense, pollinator attraction, and plant communication with the surrounding environment. In addition, oxime-derived products may serve as quenchers of reactive oxygen species and storage compounds for reduced nitrogen that may be released on demand by the activation of endogenous turnover pathways. As highly bioactive molecules, chemically synthesized oximes have found versatile uses in many sectors of society, especially in the agro- and medical sectors. This review provides an update on the structural diversity, occurrence, and biosynthesis of oximes in plants and discusses their role as key players in plant general and specialized metabolism.
Topics: Animals; Lizards; Oximes; Plants; Volatile Organic Compounds
PubMed: 29275165
DOI: 10.1016/j.molp.2017.12.014 -
Methods in Molecular Biology (Clifton,... 2018The Warburg effect describes how most cancer cells exhibit higher-than-normal glucose consumption, not only under hypoxic conditions, but also when normal oxygen levels... (Review)
Review
The Warburg effect describes how most cancer cells exhibit higher-than-normal glucose consumption, not only under hypoxic conditions, but also when normal oxygen levels are present. Although glucose transporter 1 (GLUT1) has been found to play a key role in the cellular uptake of glucose, especially in cancer cells, where it is generally overexpressed, it has not been given consideration as a suitable target for the development of anticancer drugs. In this chapter, an example of molecular design and realization of novel GLUT1 inhibitors, including in silico modeling, chemical synthesis, and biological characterization, is provided. This process started with the identification of a focused series of oxime derivatives, originally designed as estrogen receptor (ER) ligands, which were structurally optimized in order to direct their activity towards GLUT1 and to minimize their binding to the ERs, leading to the production of efficient and selective inhibitors of glucose uptake in cancer cells.
Topics: Animals; Binding Sites; Biological Assay; Chemistry Techniques, Synthetic; Drug Design; Drug Discovery; Glucose Transport Proteins, Facilitative; Humans; Models, Molecular; Oximes; Protein Binding; Structure-Activity Relationship
PubMed: 29218520
DOI: 10.1007/978-1-4939-7507-5_8 -
Molecules (Basel, Switzerland) Feb 2022Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence,...
Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid () and ()-acetophenone -2-morpholinoethyl oxime (), which reduced the viability of HeLa cells below 20% of control at concentrations of 100-250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (-), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of ()-acetophenone -2-morpholinoethyl oxime () against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was ()-1-(benzothiophene-2-yl)ethanone -4-methoxybenzyl oxime (), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Ethers; Humans; Molecular Structure; Oximes; Spectrum Analysis; Structure-Activity Relationship
PubMed: 35209155
DOI: 10.3390/molecules27041374 -
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