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Molecules (Basel, Switzerland) Oct 2022Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of... (Review)
Review
Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of them have a cyclopenta[c]pyridine skeleton. Some compounds containing this structure are potentially bioactive medicinal agents. In this paper, seven drug candidates (-), ninety natural source products (-), thirty-seven synthesized compounds (-), as well as twenty-six key intermediates (-) were summarized. We categorized five types of MTPAs and one type of cyclopenta[c]pyridine alkaloids in all. Additionally, their possible genetic pathways were proposed. Then, the chemical transformation, biotransformation, chemical synthesis, as well as the bioactivity of MTPAs and cyclopenta[c]pyridine derivatives were analyzed and summarized. Cyclopenta[c]pyridine derivatives can be concisely and chirally synthesized, and they have shown potentials with antibacterial, insecticidal, antiviral, anti-inflammatory, and neuropharmacological activities.
Topics: Monoterpenes; Alkaloids; Molecular Structure; Pyridines; Biological Products
PubMed: 36364013
DOI: 10.3390/molecules27217187 -
International Journal of Molecular... May 2022In the context of the new life-threatening COVID-19 pandemic caused by the SARS-CoV-2 virus, finding new antiviral and antimicrobial compounds is a priority in current... (Review)
Review
In the context of the new life-threatening COVID-19 pandemic caused by the SARS-CoV-2 virus, finding new antiviral and antimicrobial compounds is a priority in current research. Pyridine is a privileged nucleus among heterocycles; its compounds have been noted for their therapeutic properties, such as antimicrobial, antiviral, antitumor, analgesic, anticonvulsant, anti-inflammatory, antioxidant, anti-Alzheimer's, anti-ulcer or antidiabetic. It is known that a pyridine compound, which also contains a heterocycle, has improved therapeutic properties. The singular presence of the pyridine nucleus, or its one together with one or more heterocycles, as well as a simple hydrocarbon linker, or grafted with organic groups, gives the key molecule a certain geometry, which determines an interaction with a specific protein, and defines the antimicrobial and antiviral selectivity for the target molecule. Moreover, an important role of pyridine in medicinal chemistry is to improve water solubility due to its poor basicity. In this article, we aim to review the methods of synthesis of pyridine compounds, their antimicrobial and antiviral activities, the correlation of pharmaceutical properties with various groups present in molecules as well as the binding mode from Molecular Docking Studies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Humans; Molecular Docking Simulation; Pandemics; Pyridines; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35628466
DOI: 10.3390/ijms23105659 -
Molecules (Basel, Switzerland) Mar 2022Derivatives based on pyridine-2-6- and furan-2,5-dicarboxamide scaffolds reveal numerous chemical properties and biological activities. This fact makes them an exciting...
Derivatives based on pyridine-2-6- and furan-2,5-dicarboxamide scaffolds reveal numerous chemical properties and biological activities. This fact makes them an exciting research topic in supramolecular and coordination chemistry and in discovering new pharmacologically-active compounds. This work aimed to obtain a series of symmetrical pyridine-2-6- and furan-2,5-dicarboxamides through a condensation reaction of the appropriate acyl chlorides and aromatic amides. Successful syntheses were confirmed with NMR spectroscopy. We solved their crystal structures for seven compounds; two pyridine and five furan derivatives. Based on our crystallographic studies, we were able to indicate supramolecular features of the crystals under investigation. Additionally, Hirshfeld surface analysis allowed us to calculate a distribution of intermolecular contacts in the dicarboxamide crystals.
Topics: Amides; Furans; Magnetic Resonance Spectroscopy; Pyridines
PubMed: 35335183
DOI: 10.3390/molecules27061819 -
Nature Communications Jan 2021Although various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual...
Although various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual modification at base-resolution. For example, to obtain both true 5-methylcytosine (5mC) and true 5-hydroxymethylcytosine (5hmC) information, the two major epigenetic modifications, it usually requires subtraction of two methods, which increases noise and requires high sequencing depth. Recently, we developed TET-assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of 5mC and 5hmC. Here we demonstrate that two sister methods, TAPSβ and chemical-assisted pyridine borane sequencing (CAPS), can be effectively used for subtraction-free and specific whole-genome sequencing of 5mC and 5hmC, respectively. We also demonstrate pyridine borane sequencing (PS) for whole-genome profiling of 5-formylcytosine and 5-carboxylcytosine, the further oxidized derivatives of 5mC and 5hmC. This work completes the set of versatile borane reduction chemistry-based methods as a comprehensive toolkit for direct and quantitative sequencing of all four cytosine epigenetic modifications.
Topics: 5-Methylcytosine; Animals; Base Sequence; Mice; Mouse Embryonic Stem Cells; Oxidation-Reduction; Pyridines; Sequence Analysis, DNA; Sulfites
PubMed: 33504799
DOI: 10.1038/s41467-021-20920-2 -
Molecules (Basel, Switzerland) Sep 2022This study investigates the mechanism of metal-free pyridine phosphination with P(OEt), PPh, and PArCF using density functional theory calculations. The results show...
This study investigates the mechanism of metal-free pyridine phosphination with P(OEt), PPh, and PArCF using density functional theory calculations. The results show that the reaction mechanism and rate-determining step vary depending on the phosphine and additive used. For example, phosphination of pyridine with P(OEt) occurs in five stages, and ethyl abstraction is the rate-determining step. Meanwhile, 2-Ph-pyridine phosphination with PPh is a four-step reaction with proton abstraction as the rate-limiting step. Energy decomposition analysis of the transition states reveals that steric hindrance in the phosphine molecule plays a key role in the site-selective formation of the phosphonium salt. The mechanism of 2-Ph-pyridine phosphination with PArCF is similar to that with PPh, and analyses of the effects of substituents show that electron-withdrawing groups decreased the nucleophilicity of the phosphine, whereas aryl electron-donating groups increased it. Finally, TfO plays an important role in the C-H fluoroalkylation of pyridine, as it brings weak interactions.
Topics: Catalysis; Electrons; Metals; Models, Theoretical; Pyridines
PubMed: 36080460
DOI: 10.3390/molecules27175694 -
Antioxidants & Redox Signaling Jan 2018Pyridine dinucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), were discovered more than 100 years ago as... (Review)
Review
SIGNIFICANCE
Pyridine dinucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), were discovered more than 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases. Recent Advances: A biochemistry renaissance in biomedical research, with its increasing focus on the metabolic pathobiology of human disease, has reignited interest in pyridine dinucleotides, which has led to new insights into the cell biology of NAD(P) metabolism, including its cellular pharmacokinetics, biosynthesis, subcellular localization, and regulation. This review highlights these advances to illustrate the importance of NAD(P) metabolism in the molecular pathogenesis of disease.
CRITICAL ISSUES
Perturbations of NAD(H) and NADP(H) are a prominent feature of human disease; however, fundamental questions regarding the regulation of the absolute levels of these cofactors and the key determinants of their redox ratios remain. Moreover, an integrated topological model of NAD(P) biology that combines the metabolic and other roles remains elusive.
FUTURE DIRECTIONS
As the complex regulatory network of NAD(P) metabolism becomes illuminated, sophisticated new approaches to manipulating these pathways in specific organs, cells, or organelles will be developed to target the underlying pathogenic mechanisms of disease, opening doors for the next generation of redox-based, metabolism-targeted therapies. Antioxid. Redox Signal. 28, 180-212.
Topics: ADP-ribosyl Cyclase 1; Adenosine Triphosphate; Biosynthetic Pathways; Catalysis; Disease Susceptibility; Energy Metabolism; Homeostasis; Humans; Hydrolysis; Intracellular Space; Male; Mitochondria; NAD; NADP; NADPH Oxidases; Nitric Oxide Synthase; Oxidation-Reduction; Pyridines; Reactive Oxygen Species; Stress, Physiological
PubMed: 28635300
DOI: 10.1089/ars.2017.7120 -
Molecules (Basel, Switzerland) Apr 2024Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted... (Review)
Review
Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper. However, copper is also known to induce the proliferation of cancer cells. In view of these contradictory results, there is a need to find the most suitable copper chelators, among which Schiff-based derivatives offer a wide range of possibilities. Gathering several metal complexes in a single, larger entity may provide enhanced properties. Among the nanometric objects suitable for such purpose are dendrimers, precisely engineered hyperbranched macromolecules, which are outstanding candidates for improving therapy and diagnosis. In this review article, we present an overview of the use of a particular Schiff base, namely pyridine-imine, linked to the surface of dendrimers, suitable for complexing copper, and the use of such dendrimer complexes in biology, in particular against cancers.
Topics: Animals; Humans; Antineoplastic Agents; Chelating Agents; Coordination Complexes; Copper; Dendrimers; Imines; Neoplasms; Pyridines; Schiff Bases
PubMed: 38675623
DOI: 10.3390/molecules29081800 -
Molecules (Basel, Switzerland) Mar 2022Pyrazolo[3,4-]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1- and 2-isomers. More than 300,000 1-pyrazolo[3,4-]pyridines... (Review)
Review
Pyrazolo[3,4-]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1- and 2-isomers. More than 300,000 1-pyrazolo[3,4-]pyridines have been described which are included in more than 5500 references (2400 patents) up to date. This review will cover the analysis of the diversity of the substituents present at positions N1, C3, C4, C5, and C6, the synthetic methods used for their synthesis, starting from both a preformed pyrazole or pyridine, and the biomedical applications of such compounds.
Topics: Pyridines
PubMed: 35408636
DOI: 10.3390/molecules27072237 -
British Journal of Pharmacology Jun 2017The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a... (Review)
Review
UNLABELLED
The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases.
LINKED ARTICLES
This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.
Topics: Animals; Anti-Inflammatory Agents; Enzyme Inhibitors; Fibrosis; Humans; Inflammation; NADPH Oxidase 1; NADPH Oxidase 2; Pyrazoles; Pyrazolones; Pyridines; Pyridones
PubMed: 27273790
DOI: 10.1111/bph.13532 -
Nature Apr 2016In the classic Diels-Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4π (diene) and 2π (dienophile) pairs of...
In the classic Diels-Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4π (diene) and 2π (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4π + 2π cycloaddition reaction that generates a different, highly reactive intermediate known as an α,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, α,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC≡N), although non-participants in aza-HDDA reactions, readily function as the 2π component in PDDA cyclizations to produce, via trapping of the α,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.
Topics: Benzene; Cyclization; Cycloaddition Reaction; Diynes; Hydrogen; Hydrogenation; Isomerism; Nitriles; Oxidation-Reduction; Pyridines; Terminology as Topic; Toluene
PubMed: 27088605
DOI: 10.1038/nature17429