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Current Drug Delivery 2020Adjuvants have been obtained empirically by trial and error experiments and today, there is a tendency to the rational design of adjuvants candidates, which will...
BACKGROUND
Adjuvants have been obtained empirically by trial and error experiments and today, there is a tendency to the rational design of adjuvants candidates, which will increasingly achieve effective and safe products. The aim of this work was to design and evaluate the compound IMR-23 derived from nitroimidazole as an immunomodulatory molecule.
MATERIALS AND METHODS
The IMR-23 molecule was obtained by a condensation reaction, cytotoxicity was tested by the sulforhodamine B assay. Adjuvanticity was evaluated and in J774A.1 cells and in the mouse model, respectively.
RESULTS
IMR-23 that did not show cytotoxicity on HeLa, Vero cells and macrophages J774A.1, was able to induce the production of molecules involved in the inflammatory process, such as cytokines and chemokines determined by ELISA, to induce the production of antibodies and to generate antigenspecific cells to ovalbumin and against the antigen GST-L1b.
CONCLUSION
These results open the possibility of further studies to obtain a proper balance of immunogenicity- toxicity in the use of IMR-23 as an adjuvant molecule.
Topics: Animals; Antibodies; Cell Line; Chlorocebus aethiops; Cytokines; Dose-Response Relationship, Drug; Drug Design; HeLa Cells; Humans; Immunologic Factors; Immunomodulation; Mice; Molecular Structure; Nitroimidazoles; Oximes; Structure-Activity Relationship; Vero Cells
PubMed: 32056525
DOI: 10.2174/1567201817666200214110442 -
Organic & Biomolecular Chemistry Nov 2015New oxime-containing acyclic nucleoside phosphonates 9-{2-[(phosphonomethyl)oximino]ethyl}adenine (1), -guanine (2) and 9-{2-[(phosphonomethyl)oximino]propyl}adenine (3)...
New oxime-containing acyclic nucleoside phosphonates 9-{2-[(phosphonomethyl)oximino]ethyl}adenine (1), -guanine (2) and 9-{2-[(phosphonomethyl)oximino]propyl}adenine (3) with wide spectrum activity against different types of viruses were synthesized. The key intermediate, diethyl aminooxymethylphosphonate, was obtained by the Mitsunobu reaction. Modified conditions for the by-product separation (without chromatography and distillation) allowed us to obtain 85% yield of the aminooxy intermediate. The impact of DBU and Cs2CO3 on the N(9)/N(7) product ratio for adenine and guanine alkylation was studied. A convenient procedure for aminooxy group detection was found. The synthesized phosphonates were tested and they appeared to display moderate activity against different types of viruses (HIV, herpes viruses in cell cultures, and hepatitis C virus in the replicon system) without toxicity up to 1000 μM.
Topics: Antiviral Agents; Humans; Nucleosides; Organophosphonates; Oximes; Virus Diseases; Viruses
PubMed: 26383895
DOI: 10.1039/c5ob01571e -
Molecules (Basel, Switzerland) Dec 2012We have demonstrated that oxime-based mixed carbonates are very effective reagents for both N-protection and peptide coupling.
We have demonstrated that oxime-based mixed carbonates are very effective reagents for both N-protection and peptide coupling.
Topics: Carbonates; Indicators and Reagents; Oximes; Peptides
PubMed: 23455569
DOI: 10.3390/molecules171214361 -
Journal of Agricultural and Food... Apr 2021To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole...
To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against . The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against , among which oxime ether compound shows the highest fungicidal activity (EC = 0.0104 μg/mL) which is higher than dimethomorph (EC = 0.1148 μg/mL) and diacetylenyl amide (EC = 0.040 μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds , , , and showed moderate to good antifungal activities against , and . Scanning electron microscopy of compound on the hyphae morphology showed that compound might cause mycelial abnormalities of .
Topics: Esters; Ether; Ethers; Fungicides, Industrial; Oximes; Structure-Activity Relationship; Thiazoles
PubMed: 33780242
DOI: 10.1021/acs.jafc.0c07581 -
Farmatsevtychnyi Zhurnal 1975
Topics: Carbazoles; Drug Interactions; Organophosphorus Compounds; Oximes
PubMed: 1225553
DOI: No ID Found -
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 -
Organic & Biomolecular Chemistry Nov 2016Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation,...
Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine.
Topics: Alkenes; Cyclization; Cycloaddition Reaction; Nitrogen Oxides; Oximes
PubMed: 27819376
DOI: 10.1039/c6ob01871h -
Bioorganic & Medicinal Chemistry Jan 2011The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e.g., atropine), an anticonvulsant (e.g., diazepam) and an...
The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e.g., atropine), an anticonvulsant (e.g., diazepam) and an acetylcholinesterase (AChE) reactivator (e.g., obidoxime). The AChE reactivator is the causal treatment of OP exposure, because it cleaves the OP moiety covalently bound to the AChE active site. In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFP and then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of π-π or cation-π interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed.
Topics: Acetylcholinesterase; Binding Sites; Catalytic Domain; Cholinesterase Reactivators; Computer Simulation; Humans; Hydrogen Bonding; Organophosphorus Compounds; Oximes; Structure-Activity Relationship
PubMed: 21215642
DOI: 10.1016/j.bmc.2010.12.021 -
Journal of Controlled Release :... Nov 2018A novel approach for brain protection against poisoning by organophosphorus agents is developed based on the combination treatment of dual delivery of two oximes....
A novel approach for brain protection against poisoning by organophosphorus agents is developed based on the combination treatment of dual delivery of two oximes. Pralidoxime chloride (2-PAM) and a novel reactivator, 6-(5-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)pentyl)-3-hydroxy picolinaldehyde oxime (3-HPA), have been loaded in solid-lipid nanoparticles (SLNs) to offer distinct release profile and systemic half-life for both oximes. To increase the therapeutic time window of both oximes, SLNs with two different compartments were designed to load each respective drug. Oxime-loaded SLNs of hydrodynamic diameter between 100 and 160 nm and negative zeta potential (-30 to -25 mV) were stable for a period of 10 months at 4 °C. SLNs displayed longer circulation time in the bloodstream compared to free 3-HPA and free 2-PAM. Oxime-loaded SLNs were suitable for intravenous (iv) administration. Paraoxon-poisoned rats (0.8 × LD) were treated with 3-HPA-loaded SLNs and 2-PAM+3-HPA-loaded SLNs at the dose of 3-HPA and 2-PAM of 5 mg/kg. Brain AChE reactivation up to 30% was slowly achieved in 5 h after administration of 3-HPA-SLNs. For combination therapy with two oximes, a time-dependent additivity and increased reactivation up to 35% were observed.
Topics: Acetylcholinesterase; Animals; Brain; Cholinesterase Inhibitors; Drug Synergism; Female; Lipids; Male; Nanoparticles; Neuroprotective Agents; Oximes; Paraoxon; Rats, Wistar
PubMed: 30308259
DOI: 10.1016/j.jconrel.2018.10.010 -
Biochemical Pharmacology Aug 1971
Topics: Animals; Chromatography, Gas; Deamination; Dextroamphetamine; In Vitro Techniques; Ketones; Male; Mass Spectrometry; Microsomes, Liver; Oximes; Rabbits; Tritium
PubMed: 5137977
DOI: 10.1016/0006-2952(71)90425-4