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Current Medicinal Chemistry 2024Imidazo[4,5-b]pyridines are amongst the oldest known heteroaromatic derivatives. Their structural similarity with purine basis has however aroused the curiosity of... (Review)
Review
Imidazo[4,5-b]pyridines are amongst the oldest known heteroaromatic derivatives. Their structural similarity with purine basis has however aroused the curiosity of biologists and resulted in the developments of innovative bioactive compounds. This review thus firstly describes the main synthetic ways currently used to produce imidazo[ 4,5-b]pyridine derivatives, and secondly gives examples of their potential, especially focusing on protein inhibition abilities, thus opening the way to applications as anti-cancer or antimicrobial agents.
Topics: Humans; Anti-Infective Agents; Pyridines; Structure-Activity Relationship
PubMed: 37170991
DOI: 10.2174/0929867330666230426111650 -
Molecules (Basel, Switzerland) Sep 2022Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of...
Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.
Topics: Antineoplastic Agents; Benzoic Acid; Cell Line, Tumor; Cell Proliferation; DNA; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esters; Humans; Leukemia; Molecular Structure; Neoplasms; Pyridines; Structure-Activity Relationship; Thiazoles
PubMed: 36234755
DOI: 10.3390/molecules27196219 -
Journal of the American Chemical Society Jun 2018The transfer of protons and electrons is key to energy conversion and storage, from photosynthesis to fuel cells. Increased understanding and control of these processes...
The transfer of protons and electrons is key to energy conversion and storage, from photosynthesis to fuel cells. Increased understanding and control of these processes are needed. A new anthracene-phenol-pyridine molecular triad was designed to undergo fast photoinduced multiple-site concerted proton-electron transfer (MS-CPET), with the phenol moiety transferring an electron to the photoexcited anthracene and a proton to the pyridine. Fluorescence quenching and transient absorption experiments in solutions and glasses show rapid MS-CPET (3.2 × 10 s at 298 K). From 5.5 to 90 K, the reaction rate and kinetic isotope effect (KIE) are independent of temperature, with zero Arrhenius activation energy. From 145 to 350 K, there are only slight changes with temperature. This MS-CPET reaction thus occurs by tunneling of both the proton and electron, in different directions. Since the reaction proceeds without significant thermal activation energy, the rate constant indicates the magnitude of the electron/proton double tunneling probability.
Topics: Anthracenes; Electrons; Fluorescence; Hydrogen Bonding; Kinetics; Molecular Structure; Phenols; Protons; Pyridines; Temperature; Ultraviolet Rays
PubMed: 29847111
DOI: 10.1021/jacs.8b04455 -
Applied and Environmental Microbiology Sep 2020Bacteria degrade nicotine mainly using pyridine and pyrrolidine pathways. Previously, we discovered a hybrid of the pyridine and pyrrolidine pathways (the VPP pathway)...
Bacteria degrade nicotine mainly using pyridine and pyrrolidine pathways. Previously, we discovered a hybrid of the pyridine and pyrrolidine pathways (the VPP pathway) in N1 and characterized its key enzyme, 6-hydroxypseudooxynicotine amine oxidase (HisD). It catalyzes oxidative deamination of 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylsemialdehyde-pyridine, which is the crucial step connecting upstream and downstream portions of the VPP pathway. We determined the crystal structure of wild-type HisD to 2.6 Å. HisD is a monomer that contains a flavin mononucleotide, an iron-sulfur cluster, and ADP. On the basis of sequence alignment and structure comparison, a difference has been found among HisD, closely related trimethylamine dehydrogenase (TMADH), and histamine dehydrogenase (HADH). The flavin mononucleotide (FMN) cofactor is not covalently bound to any residue, and the FMN isoalloxazine ring is planar in HisD compared to TMADH or HADH, which forms a 6--cysteinyl flavin mononucleotide cofactor and has an FMN isoalloxazine ring in a "butterfly bend" conformation. Based on the structure, docking study, and site-directed mutagenesis, the residues Glu60, Tyr170, Asp262, and Trp263 may be involved in substrate binding. The expanded understanding of the substrate binding mode from this study may guide rational engineering of such enzymes for biodegradation of potential pollutants or for bioconversion to generate desired products. Nicotine is a major tobacco alkaloid in tobacco waste. Pyridine and pyrrolidine pathways are the two best-elucidated nicotine metabolic pathways; N1 catabolizes nicotine via a hybrid between the pyridine and pyrrolidine pathways. The crucial enzyme, 6-hydroxypseudooxynicotine amine oxidase (HisD), links the upstream and downstream portions of the VPP pathway; however, there is little structural information about this important enzyme. In this study, we determined the crystal structure of HisD from N1. Its basic insights about the structure may help us to guide the engineering of such enzymes for bioremediation and bioconversion applications.
Topics: Amino Acid Sequence; Bacterial Proteins; Flavin Mononucleotide; Metabolic Networks and Pathways; Nicotine; Pseudomonas; Pyridines; Pyrrolidines; Sequence Alignment
PubMed: 32737127
DOI: 10.1128/AEM.01559-20 -
STAR Protocols Dec 2022Kinases are indispensable signaling components. Radioactive-based phosphorylation assays are widely used but require specific protective equipment and safety trainings....
Kinases are indispensable signaling components. Radioactive-based phosphorylation assays are widely used but require specific protective equipment and safety trainings. Here, we present a Phos-tag-based non-radioactive kinase assay to study Arabidopsis kinase activities. We expressed and purified both kinase and substrate proteins from E. coli cells and then used the Phos-tag technology to detect the kinase activities under either different temperatures or chemical treatments. This non-radioactive approach is environmentally friendly and applicable to other kinases and organisms. For complete details on the use and execution of this protocol, please refer to Lin et al. (2022).
Topics: Phosphorylation; Arabidopsis; Escherichia coli; Pyridines; Phosphotransferases
PubMed: 36149791
DOI: 10.1016/j.xpro.2022.101717 -
Food Chemistry Mar 2023Heating of either 3,5-heptadien-2-one or 2,6-heptanedione in the presence of ammonia produced 2,6-dimethylpyridine, and also 3-methylcyclohex-2-en-1-one for the second...
Heating of either 3,5-heptadien-2-one or 2,6-heptanedione in the presence of ammonia produced 2,6-dimethylpyridine, and also 3-methylcyclohex-2-en-1-one for the second ketone. When phenolics were present, inhibition of pyridine formation was only observed in mixtures of 3,5-heptadien-2-one and resorcinol. This inhibition was due to the formation of ketone-resorcinol adducts, which were isolated and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) as 2,4-dimethyl-5,6-dihydro-4H-2,6-methanobenzo[d][1,3]dioxocin-9-ol and 1-(7-hydroxy-4-methylchroman-2-yl)propan-2-one. The other assayed phenolics increased pyridine formation. This increase was mainly observed in the presence of oxygen, at slightly basic pH values, depended on time, temperature, and the phenolic concentration, and had an activation energy of 56.8 kJ/mol for the formation of 2,6-dimethylpyridine from 2,6-heptanedione in the presence of orcinol. This increase was a consequence of the promotion by phenolics of a required aromatization step in the pyridine formation pathway. This phenolic function needs to be considered when phenolics are added to food products.
Topics: Phenol; Ketones; Phenols; Resorcinols; Pyridines
PubMed: 36252373
DOI: 10.1016/j.foodchem.2022.134554 -
Chemical & Pharmaceutical Bulletin Oct 2018A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic...
A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14, 15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity 5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21 exhibit potent cell growth inhibition, cell cycle arrest at G/M phase and pro-apoptotic inducing activities. The percentage inhibition assay of β-tubulin polymerization on HL-60 cells shows that the antitumor activity of the tested compounds appears to correlate well with its ability to inhibit β-tubulin polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA) measurement for compound 21 shows apoptotic inducing activities through significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel to down regulation of the level of survivin proteins.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Enzyme-Linked Immunosorbent Assay; HCT116 Cells; HL-60 Cells; Humans; MCF-7 Cells; Molecular Structure; Oxidative Stress; Polymerization; Pyridines; Pyrimidines; Structure-Activity Relationship; Tubulin
PubMed: 30111667
DOI: 10.1248/cpb.c18-00269 -
Environmental Health and Preventive... Sep 2021In recent years, heated tobacco products (HTPs), which are widely used in Japan, have been sold by various brands using additives such as flavors. It has been reported...
BACKGROUND
In recent years, heated tobacco products (HTPs), which are widely used in Japan, have been sold by various brands using additives such as flavors. It has been reported that the components of mainstream smoke are different from those of conventional cigarettes. In this study, we established an analytical method for furans and pyridines in the mainstream smoke, which are characteristic of HTPs and particularly harmful among the generated components, and investigated the amount of component to which the smokers are exposed.
METHODS
We established a simple analytical method for simultaneous analysis of gaseous and particulate compounds in the mainstream smoke of HTPs (IQOS, glo, ploom S) in Japan by combining a sorbent cartridge and glass fiber filter (Cambridge filter pad (CFP)). Both the sorbent cartridge and CFP were extracted using 2-propanol and analyzed via GC-MS/MS to determine the concentration of furans and pyridines generated from each HTP.
RESULTS
The results showed that the levels of target furans such as furfural, 2-furanmethanol, 2(5H)-furanone, and 5-methylfurfural tended to be higher in the mainstream smoke of glo than in standard cigarettes (3R4F). Pyridine, which is generated at a high level in 3R4F as a combustion component, and 4-ethenylpyridine (EP), which is a known marker of environmental tobacco smoke, were detected. Among these components, 2-furanmethanol and pyridine are classified as Group 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer (IARC). Therefore, it is possible that they will contribute to the health effects caused by use of HTPs.
CONCLUSIONS
Using the new collection and analytical method for furans and pyridines in the mainstream smoke of HTPs, the level of each compound to which smokers are exposed could be clarified. By comprehensively combining information on the amount of ingredients and toxicity, it will be possible to perform a more detailed calculation of the health risks of using HTPs. In addition, the components detected in this study may be the causative substances of indoor pollution through exhaled smoke and sidestream smoke; therefore, environmental research on the chemicals generated from HTPs would be warranted in future studies.
Topics: Furans; Gas Chromatography-Mass Spectrometry; Humans; Japan; Pyridines; Smoke; Tandem Mass Spectrometry; Tobacco Products
PubMed: 34517815
DOI: 10.1186/s12199-021-01008-1 -
Research in Microbiology 2015A novel strain, Pusillimonas sp. T2, which is capable of degrading nicotine, was isolated and identified. This strain could completely degrade 500 mg/L nicotine within...
A novel strain, Pusillimonas sp. T2, which is capable of degrading nicotine, was isolated and identified. This strain could completely degrade 500 mg/L nicotine within 8 h at 30 °C, pH 7.0. Six intermediates were detected and identified as 6-hydroxy-nicotine, 6-hydroxy-N-methylmyosmine, 6-hydroxypseudooxynicotine, 2,6-dihydroxypyridine, 6-hydroxy-3-succinoyl-pyridine and 2,5-dihydroxypyridine. Activities of 6-hydroxy-3-succinoyl-pyridine hydroxylase and 2,6-dihydroxypyridine hydroxylase were demonstrated in the cell extracts of strain T2, indicating that this strain may employ a novel variant of the pyridine and pyrrolidine pathways that is different from those of other species. This study provides the first evidence that Pusillimonas bacteria participate in nicotine degradation.
Topics: Base Sequence; Betaproteobacteria; Biodegradation, Environmental; China; Mixed Function Oxygenases; Nicotine; Phylogeny; Pyridines; Pyrrolidines; Sewage; Succinates
PubMed: 25546833
DOI: 10.1016/j.resmic.2014.12.009 -
Acta Poloniae Pharmaceutica May 2017A novel series of pyridine and triazolopyridine derivatives have been synthesized (1-17) and characterized on the basis of their elemental analyses and spectral data. In... (Comparative Study)
Comparative Study
A novel series of pyridine and triazolopyridine derivatives have been synthesized (1-17) and characterized on the basis of their elemental analyses and spectral data. In vitro antibacterial, antifungal and antioxidant evaluation were carried out for most of the new products. Compounds 3, 5b, 6c, 6d and 13 showed promising growth inhibition against Candida albicans and Aspergillus niger comparable to fluconazole as a reference antifungal drug. Furthermore, the derivatives 5d, 6c, 6d and 9 showed higher scavenging activity (99.4, 97.2, 94.8 and 90%) than that of ascorbic acid (86.4%) towards the DPPH radicals.
Topics: Antifungal Agents; Antioxidants; Aspergillus niger; Biphenyl Compounds; Candida albicans; Disk Diffusion Antimicrobial Tests; Drug Discovery; Microbial Viability; Molecular Structure; Picrates; Pyridines; Structure-Activity Relationship; Technology, Pharmaceutical; Triazoles
PubMed: 29513955
DOI: No ID Found