Review

Authors: Xuejian Zhang, Feiyan Tao, Tao Cui...

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

Authors: Anna Puckowska, Magdalena Gawel, Marlena Komorowska...

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

Review

Authors: Ana Donaire-Arias, Ana Maria Montagut, Raimon Puig de la Bellacasa...

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

Authors: Yibin Liu, Zhiyuan Hu, Jingfei Cheng...

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

Review

Authors: Maria Marinescu, Claudia-Valentina Popa

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

Review

Authors: Yong Ling, Zhi-You Hao, Dong Liang...

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

Topics: Animals; Chemistry, Pharmaceutical; Dihydropyridines; Drug Design; Drug Development; Humans; Pyridines; Structure-Activity Relationship

PubMed: 34675489
DOI: 10.2147/DDDT.S329547

Review

Authors: Malwina Krause, Henryk Foks, Katarzyna Gobis...

The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc. The collective results of biochemical and biophysical properties foregrounded their medicinal significance in central nervous system, digestive system, cancer, inflammation, etc. In recent years, new preparative methods for the synthesis of imidazopyridines using various catalysts have been described. The present manuscript to the best of our knowledge is the complete compilation on the synthesis and medicinal aspects of imidazo[4,5-]pyridines and imidazo[4,5-]pyridines reported from the year 2000 to date, including structure-activity relationships.

Topics: Catalysis; Humans; Imidazoles; Metabolic Networks and Pathways; Molecular Structure; Pyridines; Structure-Activity Relationship

PubMed: 28273868
DOI: 10.3390/molecules22030399

Review

Authors: Tehreem Tahir, Muhammad Ashfaq, Muhammad Saleem...

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

Review

Authors: Joshua P Fessel, William M Oldham

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

Review

Authors:

Topics: Animals; Carcinogenicity Tests; Carcinogens; Disease Models, Animal; Environmental Exposure; Female; Humans; Maximum Allowable Concentration; Neoplasms; Pyridines; Reproduction

PubMed: 11100414
DOI: No ID Found