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Molecules (Basel, Switzerland) Oct 2020Currently, rapid evaluation of the physicochemical parameters of drug candidates, such as lipophilicity, is in high demand owing to it enabling the approximation of the...
Currently, rapid evaluation of the physicochemical parameters of drug candidates, such as lipophilicity, is in high demand owing to it enabling the approximation of the processes of absorption, distribution, metabolism, and elimination. Although the lipophilicity of drug candidates is determined using the shake flash method (-octanol/water system) or reversed phase liquid chromatography (RP-LC), more biosimilar alternatives to classical lipophilicity measurement are currently available. One of the alternatives is immobilized artificial membrane (IAM) chromatography. The present study is a continuation of our research focused on physiochemical characterization of biologically active derivatives of isoxazolo[3,4-]pyridine-3(1)-ones. The main goal of this study was to assess the affinity of isoxazolones to phospholipids using IAM chromatography and compare it with the lipophilicity parameters established by reversed phase chromatography. Quantitative structure-retention relationship (QSRR) modeling of IAM retention using differential evolution coupled with partial least squares (DE-PLS) regression was performed. The results indicate that in the studied group of structurally related isoxazolone derivatives, discrepancies occur between the retention under IAM and RP-LC conditions. Although some correlation between these two chromatographic methods can be found, lipophilicity does not fully explain the affinities of the investigated molecules to phospholipids. QSRR analysis also shows common factors that contribute to retention under IAM and RP-LC conditions. In this context, the significant influences of WHIM and GETAWAY descriptors in all the obtained models should be highlighted.
Topics: 1-Octanol; Antifungal Agents; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Membranes, Artificial; Phospholipids; Pyridines; Pyridones; Water
PubMed: 33092252
DOI: 10.3390/molecules25204835 -
Water Science and Technology : a... Apr 2024The sp. BN6-4 capable of degrading high concentrations of pyridine was isolated from the coking sludge. The removal rate of BN6-4 to 1,000 mg/L pyridine during 48 h was...
The sp. BN6-4 capable of degrading high concentrations of pyridine was isolated from the coking sludge. The removal rate of BN6-4 to 1,000 mg/L pyridine during 48 h was 97.49 ±1.59%. The primary intermediate metabolites of pyridine degradation by strain BN6-4 were identified by gas chromatography-mass spectrometry (GC-MS), including N-Ethylurea, acetamidoacetaldehyde, and N-Hydroxymethylacetamide, etc Subsequently, two different biodegradation pathways of pyridine were proposed. First, the hydroxylation of pyridine to form the intermediates pyridin-2(1H)-one and 5,6-dihydropyridine-2,5-diol, the former undergoing oxidative ring opening and the latter oxidative ring opening via N-C2 and C2-C3 ring opening to ammonia and carbon dioxide. Furthermore, the organic matter was greatly degraded by the bioremediation of real coking wastewater using BN6-4. This study enriched the microbial resource for pyridine degradation and provided new insights about the biodegradation pathway of pyridine, which is of great significance for the pyridine pollution control and coking wastewater treatment.
Topics: Pyridines; Biodegradation, Environmental; Water Pollutants, Chemical; Sewage
PubMed: 38678405
DOI: 10.2166/wst.2024.108 -
Journal of Inorganic Biochemistry May 2022Molybdenum in redox non-innocent ligand environments features prominently in biological inorganic systems. While Holm and coworkers, along with many other researchers,...
Molybdenum in redox non-innocent ligand environments features prominently in biological inorganic systems. While Holm and coworkers, along with many other researchers, have thoroughly investigated formally high-oxidation-state molybdenum (Mo(IV)-Mo(VI)) ligated by dithiolenes, less is known about molybdenum in other formal oxidation states and/or different redox-active ligand environments. This work focuses on the investigation of low-valent molybdenum in four different redox non-innocent nitrogen ligand type environments (mononucleating and dinucleating iminopyridine, mononucleating and dinucleating bis(imino)pyridine). The reaction of iminopyridine N-(2,6-diisopropylphenyl)-1-(pyridin-2-yl)methanimine (L) with Mo(CO)(NCMe) produced Mo(L)(CO)(NCMe). Mo(L)(CO)(NCMe) undergoes transformation to Mo(L)(CO) upon treatment with CS or prolonged stirring in dichloromethane. The reaction of the open-chain dinucleating bis(iminopyridine) ligand N,N'-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-4,5-diyl)bis(1-(pyridin-2-yl)methanimine) (L) similarly produced an hexacarbonyl complex Mo(L)(CO)(NCMe) which also underwent transformation to the octacarbonyl Mo(L)(CO). Both complexes featured anti-parallel geometry of the chelating units. The oxidation of Mo(L)(CO)(NCMe) with I resulted in Mo(L)(CO)I. The reaction of mononucleating potentially tridentate bis(imino)pyridine ligand (L) (N-mesityl-1-(6-((E)-(mesitylimino)methyl)pyridin-2-yl)methanimine) with both Mo(CO)(NCMe) and Mo(CO)(NCMe) produced complexes Mo(L)(CO)(NCMe) and Mo(L)(CO) in which L was coordinated in a bidentate fashion, with one imino sidearm unbound. The reaction of dinucleating macrocyclic di(bis(imino)pyridine) analogue (L) led to the similar chemistry of Mo(L)(CO)(NCMe) and Mo(L)(CO) complexes. Treatment of Mo(L)(CO)(NCMe) with I formed a mono(carbonyl) complex Mo(L)(CO)I in which molybdenum was formally oxidized and L underwent coordination mode change to tridentate. The electronic structures of formally Mo(0) complexes in iminopyridine and bis(imino)pyridine ligand environments were investigated by density functional theory calculations.
Topics: Crystallography, X-Ray; Electronics; Ligands; Molybdenum; Pyridines
PubMed: 35151097
DOI: 10.1016/j.jinorgbio.2022.111744 -
The Journal of Biological Chemistry May 1957
Topics: Animals; Coenzymes; Liver; Mice; NAD; Pyridines
PubMed: 13428769
DOI: No ID Found -
Molecules (Basel, Switzerland) Jun 2016Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent...
Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel "on demand" chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates.
Topics: DNA; DNA Cleavage; Esters; Ethidium; Oximes; Pyridines; Spectrum Analysis; Viscosity
PubMed: 27376258
DOI: 10.3390/molecules21070864 -
Nuclear Medicine and Biology May 2018
Topics: Animals; Aza Compounds; Bismuth; Cattle; Drug Stability; Ethers; Female; Isotope Labeling; Mice; Models, Molecular; Molecular Conformation; Pyridines; Radioisotopes; Tissue Distribution
PubMed: 29499420
DOI: 10.1016/j.nucmedbio.2018.01.005 -
International Journal of Molecular... Apr 2023About twenty molecules sharing 1-chromeno[3,2-]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl...
About twenty molecules sharing 1-chromeno[3,2-]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-]pyridin-10-ones (1,2,3,4-THCP-10-ones, ) or 2,3-dihydro-2-methyl-1-chromeno[3,2-]pyridines (2,3-DHPCs, ). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives inhibit MAO A (IC about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one , bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC 0.51 μM) and moderate inhibitor of both ChEs (ICs 7-8 μM); (iii) the 1-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog achieving MAO B IC of 3.51 μM. The MAO B inhibitor deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson's disease and neuroprotectant for Alzheimer's disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog exerts anti-tumor activity with ICs in the range 4.83-11.3 μM.
Topics: Humans; Monoamine Oxidase Inhibitors; Structure-Activity Relationship; Monoamine Oxidase; Pyridines; Cholinesterase Inhibitors
PubMed: 37175433
DOI: 10.3390/ijms24097724 -
Chemical Communications (Cambridge,... Nov 2012A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the...
A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne.
Topics: Acetates; Alkynes; Amines; Catalysis; Copper; Cyclization; Oxidation-Reduction; Pyridines; Rhodium
PubMed: 23069867
DOI: 10.1039/c2cc36699a -
Metallomics : Integrated Biometal... Aug 2012Dysregulated metal ions are hypothesized to play a role in the aggregation of the amyloid-β (Aβ) peptide, leading to Alzheimer's disease (AD) pathology. In addition to...
Dysregulated metal ions are hypothesized to play a role in the aggregation of the amyloid-β (Aβ) peptide, leading to Alzheimer's disease (AD) pathology. In addition to direct effects on Aβ aggregation, both Cu and Fe can catalyze the generation of reactive oxygen species (ROS), possibly contributing to significant neuronal toxicity. Therefore, disruption of metal-Aβ interactions has become a viable strategy for AD therapeutic development. Herein, we report a new series of dual-function triazole-pyridine ligands [4-(2-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)morpholine (L1), 3-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)propan-1-ol (L2), 2-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)acetic acid (L3), and 5-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)pentan-1-amine (L4)] that interact with the Aβ peptide and modulate its aggregation in vitro. Metal chelation and Aβ interaction properties of these molecules were studied by UV-vis, NMR spectroscopy and X-ray crystallography. In addition, turbidity and transmission electron microscopy (TEM) were employed to determine the anti-aggregation properties of L1-L4. All compounds demonstrated an ability to limit metal-induced Aβ aggregation. Overall, our studies suggest the utility of the triazole-pyridine framework in the development of chemical reagents toward inhibitors for metal-triggered Aβ aggregation.
Topics: Amyloid beta-Peptides; Crystallography, X-Ray; Hydrogen-Ion Concentration; Ligands; Magnetic Resonance Spectroscopy; Metals; Models, Molecular; Protein Structure, Quaternary; Pyridines; Solutions; Spectrophotometry, Ultraviolet; Triazoles
PubMed: 22825244
DOI: 10.1039/c2mt20113e -
Inorganic Chemistry Sep 2004Pyridine-2,4,6-tricarboxylic acid (ptcH(3)) readily reacts with a Zn(II) salt at room temperature to form different products depending upon the presence or absence of...
Pyridine-2,4,6-tricarboxylic acid (ptcH(3)) readily reacts with a Zn(II) salt at room temperature to form different products depending upon the presence or absence of pyridine in the reaction mixture. In the presence of pyridine, the ligand breaks to form infinitely zigzag coordination polymers with the empirical formula [Zn(Ox)(py)(2)]n(Ox = oxalate, py = pyridine). The backbone is formed from Zn(II)-oxalate where two pyridine molecules are coordinated to each Zn(II) ion giving it hexacoordination. The orientation of the bound pyridines is slightly different when Zn(II)-nitrate is used compared to that when Zn(II)-sulfate (or acetate) salt is used. In absence of pyridine, the ligand remains intact and forms a mixture of a carboxylate-bridged coordination polymer and a discrete carboxylate-bridged 12-membered metallomacrocycle.
Topics: Hydrogen Bonding; Ligands; Models, Chemical; Pyridines; Tricarboxylic Acids; Zinc Compounds
PubMed: 15332798
DOI: 10.1021/ic049490c