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Nature Jun 2021Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and...
Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile. Drug candidates increasingly contain trifluoromethyl (CF) and difluoromethyl (CFH) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life. New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CFX groups (where X is F or H) in complex drug-like molecules are rare. Pyridines are the most common aromatic heterocycles in pharmaceuticals, but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development. Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp-sp coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.
Topics: Alkylation; Animals; Carbon; Fluorine; Humans; Hydrogen; Ligands; Pharmaceutical Preparations; Pharmacokinetics; Phosphines; Phosphorus; Pyridines
PubMed: 33910228
DOI: 10.1038/s41586-021-03567-3 -
Molecules (Basel, Switzerland) Aug 2021Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown... (Review)
Review
Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure-activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.
Topics: Azo Compounds; Imaging, Three-Dimensional; Phenols; Pyridines
PubMed: 34443460
DOI: 10.3390/molecules26164872 -
Biometals : An International Journal on... Feb 2021The emergence of resistant bacterial strains mainly due to misuse of antibiotics has seriously affected our ability to treat bacterial illness, and the development of...
The emergence of resistant bacterial strains mainly due to misuse of antibiotics has seriously affected our ability to treat bacterial illness, and the development of new classes of potent antimicrobial agents is desperately needed. In this study, we report the efficient synthesis of a new pyrazoline-pyridine containing ligand L1 which acts as an NN-donor for the formation of a novel silver (I) complex 2. The free ligand did not show antibacterial activity. High potency was exhibited by the complex against three Gram-negative bacteria, namely Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumanii with the minimum inhibitory concentration (MIC) ranging between 4 and 16 μg/mL (4.2-16.7 μM), and excellent activity against the fungi Candida albicans and Cryptococcus neoformans (MIC ≤ 0.25 μg/mL = 0.26 μM). Moreover, no hemolytic activity within the tested concentration range was observed. In addition to the planktonic growth inhibition, the biofilm formation of both Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was significantly reduced by the complex at MIC concentrations in a dose-dependent manner for Pseudomonas aeruginosa, whereas a biphasic response was obtained for MRSA showing that the sub-MIC doses enhanced biofilm formation before its reduction at higher concentration. Finally, complex 2 exhibited strong DNA binding with a large drop in DNA viscosity indicating the absence of classical intercalation and suggesting the participation of the silver ion in DNA binding which may be related to its antibacterial activity. Taken together, the current results reveal that the pyrazoline-pyridine silver complexes are of high interest as novel antibacterial agents, justifying further in vitro and in vivo investigation.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Biofilms; Coordination Complexes; Escherichia coli; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Pyrazoles; Pyridines; Silver
PubMed: 33156436
DOI: 10.1007/s10534-020-00263-z -
International Journal of Nanomedicine 2019Aiming to produce pyridine azo disperse dyes with good fastness properties and promising antimicrobial activity, a number of novel systems of polyfunctionalized pyridine...
AIM
Aiming to produce pyridine azo disperse dyes with good fastness properties and promising antimicrobial activity, a number of novel systems of polyfunctionalized pyridine azo dyes and their selenium nanoparticles (SeNPs) were synthesized.
MATERIALS AND METHODS
The synthesized products were formed by the reaction of diazotized aniline derivatives or diazotized amino antipyrene with any of dibenzoyl methane or benzoyl acetone and cyanoacetamide in boiling ethanolic sodium ethoxide. The structures of the newly synthesized compounds were elucidated by elemental analysis and spectral data. Moreover, (SeNPs) of the pyridine azo disperse dyes were characterized by Ultra-Violet -Visible spectrophotometry, dynamic light scattering , X-ray diffraction, and transmission electron microscope analysis. On the other hand, the synthesized dyes and its (SeNPs) were applied for disperse dyeing of nylon 66 and their fastness properties were measured, such as washing, rubbing, perspiration, and light fastness. In addition, the antimicrobial activities for all the synthesized compounds and for (SeNPs) prepared compounds () were evaluated.
RESULTS
Compounds , and were the most active compounds against all Gram-positive and Gram-negative bacterial species. While, compounds , and were the most active toward some of the bacterial strains (at least two from the selected four strains). Moreover, compounds showed higher activity toward the fungal strain. Also, the minimal inhibitory concentrations for all the most active compounds were determined.
CONCLUSION
Finally, all the (SeNPs) compounds revealed higher activity against bacterial and fungal strains than the other synthesized compounds.
Topics: Anti-Bacterial Agents; Azo Compounds; Bacteria; Fungi; Metal Nanoparticles; Microbial Sensitivity Tests; Pyridines; Selenium; X-Ray Diffraction
PubMed: 31632007
DOI: 10.2147/IJN.S216914 -
Journal of the American Chemical Society Feb 2021Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While...
Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.
Topics: Boranes; Catalysis; Oxidation-Reduction; Pyridines
PubMed: 33471541
DOI: 10.1021/jacs.0c12479 -
Archiv Der Pharmazie May 2021Nine novel hydrazone derivatives (4a-i) incorporating pyridine and isatin moieties were synthesized through one-pot, four-component heterocyclic condensation reactions....
Nine novel hydrazone derivatives (4a-i) incorporating pyridine and isatin moieties were synthesized through one-pot, four-component heterocyclic condensation reactions. The structures of all new compounds (2a-e, 3a, 3c-e, and 4a-e) were identified by H nuclear magnetic resonance (NMR), C NMR, and Fourier-transform infrared spectroscopic techniques and elemental analysis. Cell viability assays for the tested hydrazone derivatives were performed and the log IC values of the compounds were calculated after a 24-h treatment. All hydrazide derivatives tested showed a promising antitumor activity against A-2780 cells as compared with the standard drug docetaxel with a log IC value of 0.2200 μM (p < .05). Seven of the examined compounds (4b-e, 4g-i) showed high cytotoxic activity against A-2780 cells as compared with the standard drug docetaxel. Whereas the log IC of docetaxel was 0.2200 μM for A-2780 cells at 24 h, the IC values of these compounds were -0.4987, -0.4044, -0.8138, -0.3868, -0.6954, -0.4751, and 0.1809 μM, respectively. Three of the compounds, 4b, 4d, and 4i, showed high cytotoxic activity against MCF-7 cells as compared with docetaxel (p < .05). Whereas the log IC of docetaxel was 0.2400 μM for MCF-7 cells at 24 h, the log IC values of compounds 4b, 4d, and 4i were -0.1293, -0.1700, and 0.2459 μM, respectively.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Hydrazones; Isatin; Molecular Structure; Pyridines; Structure-Activity Relationship
PubMed: 33368627
DOI: 10.1002/ardp.202000377 -
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 -
Bioorganic & Medicinal Chemistry Letters Aug 2021In the United States, approximately one million individuals are hospitalized every year for arrhythmias, making arrhythmias one of the top causes of healthcare...
In the United States, approximately one million individuals are hospitalized every year for arrhythmias, making arrhythmias one of the top causes of healthcare expenditures. Mexiletine is currently used as an antiarrhythmic drug but has limitations. The purpose of this work was to use normal and Long QT syndrome Type 3 (LQTS3) patient-derived human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to identify an analog of mexiletine with superior drug-like properties. Compared to racemic mexiletine, medicinal chemistry optimization of substituted racemic pyridyl phenyl mexiletine analogs resulted in a more potent sodium channel inhibitor with greater selectivity for the sodium over the potassium channel and for late over peak sodium current.
Topics: Cardiac Conduction System Disease; Dose-Response Relationship, Drug; Humans; Induced Pluripotent Stem Cells; Long QT Syndrome; Mexiletine; Molecular Structure; Myocytes, Cardiac; NAV1.5 Voltage-Gated Sodium Channel; Pyridines; Structure-Activity Relationship
PubMed: 34062251
DOI: 10.1016/j.bmcl.2021.128162 -
Journal of Agricultural and Food... Oct 2019Venomous imported fire ants cause significant medical problems. Alkaloids are an important component of imported fire ant venom. Piperidine and piperideine alkaloids...
Venomous imported fire ants cause significant medical problems. Alkaloids are an important component of imported fire ant venom. Piperidine and piperideine alkaloids have been identified in fire ant venom. In this study, we studied the venom alkaloids of the red imported fire ant, Buren, the black imported fire ant, Forel, and the hybrid, × . Pyridine alkaloids were detected the first time in fire ants using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (SPME-GC-MS). The thermal desorption process was manipulated to facilitate the isolation and identification of pyridine alkaloids that were coeluted with piperidine or piperideine alkaloids in GC. After SPME extraction of ant venom, we conducted a series of consecutive GC-MS injections, each with a partial desorption. Hidden pyridine alkaloid peaks were revealed after the overlapping piperidine or piperidiene alkaloid peaks had been desorbed. Using this approach, 10 2-methyl-6-alkyl (or alkenyl)pyridines (-) were found the first time in the venom of imported fire ants. Structures of three pyridine alkaloids were confirmed by synthesis, including 2-methyl-6-undecylpyridine (), 2-methyl-6-tridecylpyridine (), and 2-methyl-6-pentadecylpyridine (). We also developed a silica gel column chromatography method to separate the pyridine alkaloids from other alkaloids. Using column chromatography and GC-MS with single ion monitoring at 107 /, five pyridine alkaloids were quantified for both workers and female alates of and .
Topics: Alkaloids; Animals; Ant Venoms; Ants; Female; Gas Chromatography-Mass Spectrometry; Molecular Structure; Pyridines; Solid Phase Microextraction
PubMed: 31536348
DOI: 10.1021/acs.jafc.9b03631 -
Bioorganic Chemistry Jan 2020A novel series of the 2-pyridine substituted 3a-e and 4-pyridine substituted 4a-e thiazole derivatives were synthesized, characterized, and evaluated for the biological...
A novel series of the 2-pyridine substituted 3a-e and 4-pyridine substituted 4a-e thiazole derivatives were synthesized, characterized, and evaluated for the biological activity. Crystallographic parameters and inter- and intramolecular interactions of 3a and 3c single crystals were examined through XRD analysis. The chemical reactivity potentials of the compounds were evaluated, by comparing with a theoretical approach based on DFT. The biological activity properties of synthesized compounds were determined by antimicrobial activity with Gram positive, Gram negative, Yeast via minimal inhibitory concentration (MIC) method and DNA cleavage activity studies. The most obvious findings to emerge from this study are that on the basis of both biological activity and chemical reactivity 4-pyridine thiazole hybrid compounds 4a-e showed more potent activity than 3a-e. In general, the antimicrobial activity of synthesized compounds follows the Bacillus cereus > Staphylococcus aureus > Candida albicans > Escherichia coli > Pseudomonas aeruginosa. The most potent compound 4c (MIC values 0.02 mM) exhibited antimicrobial activity against Staphylococcus aureus and Bacillus cereus. Furthermore, this compound has a good electrophilicity index value (4.56 eV).
Topics: Anti-Bacterial Agents; Antifungal Agents; Bacillus cereus; Candida albicans; DNA Cleavage; DNA, Bacterial; Density Functional Theory; Dose-Response Relationship, Drug; Escherichia coli; Molecular Structure; Pseudomonas aeruginosa; Pyridines; Staphylococcus aureus; Structure-Activity Relationship; Thiazoles
PubMed: 31838288
DOI: 10.1016/j.bioorg.2019.103476