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Critical Reviews in Analytical Chemistry 2024Pyridine derivatives are the most common and significant heterocyclic compounds, which play an important role in various fields ranging from medicinal to chemosensing... (Review)
Review
Pyridine derivatives are the most common and significant heterocyclic compounds, which play an important role in various fields ranging from medicinal to chemosensing applications. Pyridine derivatives possess different biological activities such as antifungal, antibacterial, antioxidant, antiglycation, analgesic, antiparkinsonian, anticonvulsant, anti-inflammatory, ulcerogenic, antiviral, and anticancer activity. Furthermore, these derivatives have a high affinity for various ions and neutral species and can be used as a highly effective chemosensor for the determination of different species. In this review article, generally used synthetic routes of pyridine, structural characterization, medicinal applications, and potential of pyridine derivatives in analytical chemistry as chemosensors have been discussed. We hope this study will support the new thoughts to design biological active compounds and highly selective and effective chemosensors for the detection of various species (anions, cations, and neutral species) in various samples (environmental, agricultural, and biological). [Figure: see text].
Topics: Pyridines; Humans; Animals
PubMed: 35724248
DOI: 10.1080/10408347.2022.2089839 -
Chemical Biology & Drug Design Sep 2022Among the various heterocyclic molecules employed for drug design and discovery, pyrazolopyridine is one of the promising pharmacophores. Pyrazolopyridine is a result of... (Review)
Review
Among the various heterocyclic molecules employed for drug design and discovery, pyrazolopyridine is one of the promising pharmacophores. Pyrazolopyridine is a result of fusion of pyrazole and pyridine rings. The potent pharmacology of pyrazolopyridine may be the synergistic effect of pyrazole and pyridine moieties in a single framework. It has been used in drug design of a wide range of diseases such as anticancer, antimicrobial, anti-inflammatory, and neuroprotection. Cancer has become a common disease among elderly people now a days that might be because of genetic inheritance to some extent, carcinogens, pollution, and some infectious diseases. Whatever may be the reason, cancer is one of the major causes of deaths worldwide. In addition, over-usage and improper usage of antibiotics have led to drug resistance of microbes. Further, inflammation is a cause of various diseases such as arthritis, and other diseases. Thus, proinflammatory kinases are considered as primary target for inhibition of inflammation. In view of this, a work that compiles potent pharmacology of recently reported pyrazolopyridine analogs has been planned. The review is aimed to discuss pharmacology in brief along with structure-activity relationship (SAR). The review would emphasize importance of pyrazolopyridines in future drug design and discovery and may help in design of potent pharmacological agents.
Topics: Aged; Drug Design; Humans; Inflammation; Molecular Structure; Pyrazoles; Pyridines; Structure-Activity Relationship
PubMed: 35661410
DOI: 10.1111/cbdd.14098 -
Journal of Agricultural and Food... Dec 2022We designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds exhibited good insecticidal...
We designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds exhibited good insecticidal and antiviral activities. Notably, the series of compounds displayed good insecticidal activity against . Compounds (EC = 63.68 mg/L) and (EC = 47.81 mg/L) exhibited inactivation activities against the tobacco mosaic virus (TMV), which were similar to that of Ningnanmycin (EC = 58.01 mg/L). Molecular docking showed that compounds and exhibited satisfactory affinities for the TMV coat protein (TMV-CP), with binding energies (-6.7 and -6.4 kcal/mol, respectively) slightly lower than that of Ningnanmycin (-6.3 kcal/mol). Further, molecular dynamics analysis revealed that compounds and exhibited better binding stability values than Ningnanmycin. Microscale thermophoresis showed that compounds ( = 0.053 ± 0.016 μM) and ( = 0.045 ± 0.022 μM) bound more strongly to TMV-CP than Ningnanmycin ( = 0.10 ± 0.029 μM). The results of transmission electron microscopy showed that these two compounds hindered the self-assembly and growth of TMV. In summary, we showed that these pyridine spiro derivatives could be used as a basis for the research and development of novel pesticides.
Topics: Structure-Activity Relationship; Molecular Docking Simulation; Tobacco Mosaic Virus; Pyridines; Antiviral Agents; Drug Design
PubMed: 36475721
DOI: 10.1021/acs.jafc.2c06189 -
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 -
Chemical Record (New York, N.Y.) Mar 2022C-H activation and functionalization is quite promising in recent days as the strategy offers a go-to general method for different bond formations and hence grants... (Review)
Review
C-H activation and functionalization is quite promising in recent days as the strategy offers a go-to general method for different bond formations and hence grants synthetic versatility. At the same time, imidazopyridine, a fused bicycle of imidazole moiety with pyridine ring, has a profound impact due to its ubiquitous and prodigious application in medicinal as well as material chemistry. The presence of N-1 atom in 2-arylImidazo[1,2-a]pyridine facilitates the coordination with metal catalysts leading to the formation of ortho-substituted products. This review summarizes all the articles on ortho C-H functionalization of 2-arylImidazo[1,2-a]pyridines published till August 2021.
Topics: Catalysis; Metals; Pyridines
PubMed: 34757691
DOI: 10.1002/tcr.202100240 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2022Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This...
Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X-ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid-state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen-bond-directed receptor that can be tuned for complementary hydrogen bonding.
Topics: Hydrogen Bonding; Nitrogen; Phosphorus; Pyridines
PubMed: 35213751
DOI: 10.1002/chem.202200472 -
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 -
Anti-cancer Agents in Medicinal... 2023Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and accounts for ~90% of cases, with an approximated incidence of >1 million cases by 2025.... (Review)
Review
OBJECTIVES
Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and accounts for ~90% of cases, with an approximated incidence of >1 million cases by 2025. Currently, the backbone of HCC therapy is the oral multi-kinase inhibitor, Sorafenib, which consists of a Pyridine heterocycle ring system. This review highlights the introspective characteristics of seven anticancer drugs of heterocyclic nature against HCC along with their structural activity relationships and molecular targets.
METHODS
Literature collection was performed using PubMed, Google Scholar, SCOPUS, and Cross ref. Additional information was taken from the official website of the FDA and GLOBOCAN. Key findings/ Results: Based on the available literature, approved heterocyclic compounds show promising results against HCC, including Sorafenib (Pyridine), Regorafenib (Pyridine), Lenvatinib (Quinoline), Cabozantinib (Quinoline), Gemcitabine (Pyrimidine), 5-Fluorouracil (Pyrimidine)and Capecitabine (Pyrimidine), their mechanism of action and key aspects regarding its structural activity were included in the review.
CONCLUSION
Heterocyclic compounds represent almost two-thirds of the novel drugs approved by FDA between 2010 and 2020 against Cancer. This review summarizes the clinical relevance, mechanism of action, structural activity relationship, and challenges of the seven available anticancer drugs with heterocyclic ring systems against HCC.
Topics: Humans; Carcinoma, Hepatocellular; Sorafenib; Liver Neoplasms; Phenylurea Compounds; Antineoplastic Agents; Pyridines; Quinolines; Pyrimidines
PubMed: 35440316
DOI: 10.2174/1871520622666220418115310