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Drug Design, Development and Therapy 2021Pyridine-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... (Review)
Review
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 -
Molecules (Basel, Switzerland) Dec 2022Chromeno[2,3-]pyridines are substances demanded in medicinal and material chemistry. (pot, atom, and step economy) and in particular approaches are key green chemistry...
Chromeno[2,3-]pyridines are substances demanded in medicinal and material chemistry. (pot, atom, and step economy) and in particular approaches are key green chemistry techniques that are applied for the synthesis of heterocyclic compounds. In this case, the approach was extended with 'component economy', as solvent was used also as reactant (solvent-involved reaction). This approach was adopted for the synthesis of previously unknown -substituted 5-alkoxy-5-chromeno[2,3-]pyridines via transformation, namely the reaction of salicylaldehydes and malononitrile dimer, with the subsequent addition of alcohol. The mechanistic studies revealed the possibility of concurrent reaction. The studies aided in optimizing the reaction conditions for the best yields (77-93%). Thus, the reaction proceeds efficient and quickly, and the work-up procedure (only simple filtering) is very convenient. The structure of synthesized chromeno[2,3-]pyridines was confirmed by 2D NMR spectroscopy.
Topics: Pyridines; Solvents; Ethanol; Heterocyclic Compounds
PubMed: 36615259
DOI: 10.3390/molecules28010064 -
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 2017The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential... (Review)
Review
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 -
Molecules (Basel, Switzerland) Jan 2020An increasing interest in the synthesis and use of optically active pyridine -oxides as chiral controllers for asymmetric reactions has been observed in the last few... (Review)
Review
An increasing interest in the synthesis and use of optically active pyridine -oxides as chiral controllers for asymmetric reactions has been observed in the last few years. Chiral heteroaromatic -oxides can work as powerful electron-pair donors, providing suitable electronic environments in the transition state formed within the reaction. The nucleophilicity of the oxygen atom in -oxides, coupled with a high affinity of silicon to oxygen, represent ideal properties for the development of synthetic methodology based on nucleophilic activation of organosilicon reagents. The application of chiral -oxides as efficient organocatalysts in allylation, propargylation, allenylation, and ring-opening of meso-epoxides, as well as chiral ligands for metal complexes catalyzing Michael addition or nitroaldol reaction, can also be found in the literature. This review deals with stereoselective applications of -oxides, and how the differentiating properties are correlated with their structure. It contains more recent results, covering approximately the last ten years. All the reported examples have been divided into five classes, according to the chirality elements present in their basic molecular frameworks.
Topics: Catalysis; Heterocyclic Compounds; Pyridines
PubMed: 31947566
DOI: 10.3390/molecules25020330 -
Scientific Reports Apr 2023Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules...
Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.
Topics: Female; Humans; Breast Neoplasms; Cell Cycle Checkpoints; Apoptosis; Caspases; Antineoplastic Agents; MCF-7 Cells; Reactive Oxygen Species; Pyrazoles; Pyridines; Naphthyridines; Cell Proliferation; Cell Line, Tumor
PubMed: 37005457
DOI: 10.1038/s41598-023-32489-5 -
Tuberculosis (Edinburgh, Scotland) Jul 2021Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well...
Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of the pyridyl nitrogen atom, isomerization of the pyridine nitrogen to other positions, replacement of the pyridine ring with isosteric heterocycles, and modification of the hydrazide moiety of INH abolishes antitubercular activity. Similarly, substitution of the pyridine ring at the 3-position is not tolerated while substitution at the 2-position is permitted with 2-methyl-INH 9 displaying antimycobacterial activity comparable to INH. To assess the specific activity of this series of INH analogs against mycobacteria, we assayed them against a panel of gram-positive and gram-negative bacteria, as well as a few fungi. As expected INH and its analogs display a narrow spectrum of activity and are inactive against all non-mycobacterial strains evaluated, except for 4, which has modest inhibitory activity against Cryptococcus neoformans. Our findings provide an updated analysis of the structure-activity relationship of INH that we hope will serve as useful resource for the community.
Topics: Antitubercular Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Isoniazid; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Pyridines; Structure-Activity Relationship
PubMed: 34116482
DOI: 10.1016/j.tube.2021.102100 -
International Journal of Environmental... Oct 2022The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of...
The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.
Topics: Male; Humans; Adult; Methemoglobinemia; Methylene Blue; Anemia, Hemolytic; Pyridines; Neurotoxicity Syndromes; Poisoning
PubMed: 36360910
DOI: 10.3390/ijerph192114031 -
Future Medicinal Chemistry Feb 2020Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Two new...
Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Two new classes of -(imidazole/benzimidazole)-pyridine derivatives were designed, synthesized and evaluated for their antimycobacterial activity. The synthesis is efficient and straightforward, involving only two successive -alkylations. The anti-TB assay reveal that our compounds have an excellent anti-TB activity against both replicating and nonreplicating , are not cytotoxic, exhibited a very good intracellular activity and are active against drug-resistant strains, some compounds have a bactericidal mechanism. The absorption, distribution, metabolism, excretion and toxicity studies performed for one compound are promising, indicating that it is a good candidate for a future drug.
Topics: Anti-Bacterial Agents; Benzimidazoles; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyridines; Tuberculosis
PubMed: 31916456
DOI: 10.4155/fmc-2019-0063 -
Molecules (Basel, Switzerland) Jun 2023Fe[CHN][N(CN)] () was synthesized from a reaction of stoichiometric amounts of NaN(CN) and FeCl·4HO in a methanol/pyridine solution. Single-crystal and powder...
Fe[CHN][N(CN)] () was synthesized from a reaction of stoichiometric amounts of NaN(CN) and FeCl·4HO in a methanol/pyridine solution. Single-crystal and powder diffraction show that crystallizes in the monoclinic space group 2/ (no. 12), different from Mn[CHN][N(CN)] (2/, no. 14) due to tilted pyridine rings, with = 7.453(7) Å, = 13.167(13) Å, = 8.522(6) Å, = 114.98(6)° and = 2. ATR-IR, AAS, and CHN measurements confirm the presence of dicyanamide and pyridine. Thermogravimetric analysis shows that π-stacking interactions of the pyridine rings play an important role in structural stabilization. Based on DFT-optimized structures, a chemical bonding analysis was performed using a local-orbital framework by projection from a plane-wave basis. The resulting bond orders and atomic charges are in good agreement with the expectations based on the structure analysis. SQUID magnetic susceptibility measurements show a high-spin state Fe compound with predominantly antiferromagnetic exchange interactions at lower temperatures.
Topics: Iron; Models, Molecular; Pyridines
PubMed: 37446550
DOI: 10.3390/molecules28134886