-
Mini Reviews in Medicinal Chemistry 2022The incidence of cancer is increasing worldwide, affecting a vast majority of the human population, therefore, new different anticancer agents are being developed now... (Review)
Review
The incidence of cancer is increasing worldwide, affecting a vast majority of the human population, therefore, new different anticancer agents are being developed now and their safety still needs to be evaluated. Among them, pyridine based drugs are contributing a lot, as they are one of the imperative pharmacophores occurring synthetically as well as naturally in heterocyclic compounds, having a wide-range of therapeutic applications in the area of drug discovery that offers many chances for further improvement in antitumor agents via acting onto numerous receptors of extreme prominence. Many pyridine derivatives are reported to inhibit enzymes, receptors and many other targets for controlling and curing the global health issue of cancer. Nowadays in combination with other moieties, researchers are focusing on the development of pyridine-based new derivatives for cancer treatment. Therefore, this review sheds light on the recent therapeutic expansion of pyridine together with its molecular docking, structure-activity-relationship, availability in the market, a summary of recently patented and published research works that shall jointly help the scientists to produce effective drugs with the desired pharmacological activity.
Topics: Antineoplastic Agents; Humans; Molecular Docking Simulation; Molecular Structure; Neoplasms; Pyridines; Structure-Activity Relationship
PubMed: 34126914
DOI: 10.2174/1389557521666210614162031 -
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 -
Mini Reviews in Medicinal Chemistry 2019At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of... (Review)
Review
At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of cancer-related mortality accounting for approximately 15% of all cancer cases worldwide. While Non-Small Cell Lung Carcinomas (NSCLCs) makes up to 80% of lung cancer cases. The patient compliance has been weakening because of serious drug resistance and adverse drug effects. Therefore, there is an urgent need for the development of novel structural agents to inhibit NSCLCs. Nitrogen-containing heterocyclic compounds exhibit wide range of biological properties, especially antitumor activity. We reviewed some deadly defects of clinical medicines for the lung cancer therapy and importance of nitrogen based heterocyclic derivatives against NSCLCs. Nitrogen heterocycles exhibit significant antitumor activity against NSCLCs. Nitrogen heterocyclic hybrids could be developed as multi-target-directed NSCLC inhibitors and it is believed that the review is significant for rational designs and new ideas in the development of nitrogen heterocyclic-based drugs.
Topics: Antineoplastic Agents; Azoles; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Drug Resistance, Neoplasm; Heterocyclic Compounds; Humans; Lung Neoplasms; Nitrogen; Pyridines
PubMed: 30864519
DOI: 10.2174/1389557519666190312152358 -
Journal of Inorganic Biochemistry May 2022Molybdenum in redox non-innocent ligand environments features prominently in biological inorganic systems. While Holm and coworkers, along with many other researchers,...
Molybdenum in redox non-innocent ligand environments features prominently in biological inorganic systems. While Holm and coworkers, along with many other researchers, have thoroughly investigated formally high-oxidation-state molybdenum (Mo(IV)-Mo(VI)) ligated by dithiolenes, less is known about molybdenum in other formal oxidation states and/or different redox-active ligand environments. This work focuses on the investigation of low-valent molybdenum in four different redox non-innocent nitrogen ligand type environments (mononucleating and dinucleating iminopyridine, mononucleating and dinucleating bis(imino)pyridine). The reaction of iminopyridine N-(2,6-diisopropylphenyl)-1-(pyridin-2-yl)methanimine (L) with Mo(CO)(NCMe) produced Mo(L)(CO)(NCMe). Mo(L)(CO)(NCMe) undergoes transformation to Mo(L)(CO) upon treatment with CS or prolonged stirring in dichloromethane. The reaction of the open-chain dinucleating bis(iminopyridine) ligand N,N'-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-4,5-diyl)bis(1-(pyridin-2-yl)methanimine) (L) similarly produced an hexacarbonyl complex Mo(L)(CO)(NCMe) which also underwent transformation to the octacarbonyl Mo(L)(CO). Both complexes featured anti-parallel geometry of the chelating units. The oxidation of Mo(L)(CO)(NCMe) with I resulted in Mo(L)(CO)I. The reaction of mononucleating potentially tridentate bis(imino)pyridine ligand (L) (N-mesityl-1-(6-((E)-(mesitylimino)methyl)pyridin-2-yl)methanimine) with both Mo(CO)(NCMe) and Mo(CO)(NCMe) produced complexes Mo(L)(CO)(NCMe) and Mo(L)(CO) in which L was coordinated in a bidentate fashion, with one imino sidearm unbound. The reaction of dinucleating macrocyclic di(bis(imino)pyridine) analogue (L) led to the similar chemistry of Mo(L)(CO)(NCMe) and Mo(L)(CO) complexes. Treatment of Mo(L)(CO)(NCMe) with I formed a mono(carbonyl) complex Mo(L)(CO)I in which molybdenum was formally oxidized and L underwent coordination mode change to tridentate. The electronic structures of formally Mo(0) complexes in iminopyridine and bis(imino)pyridine ligand environments were investigated by density functional theory calculations.
Topics: Crystallography, X-Ray; Electronics; Ligands; Molybdenum; Pyridines
PubMed: 35151097
DOI: 10.1016/j.jinorgbio.2022.111744 -
Bioorganic & Medicinal Chemistry Letters Nov 2022Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities....
Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6‑aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC values in the micromolar range of 5.98-12.58 μM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G/M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.
Topics: Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fluorouracil; HeLa Cells; Humans; Molecular Structure; Pyridines; Structure-Activity Relationship; Triazoles
PubMed: 36089111
DOI: 10.1016/j.bmcl.2022.128978 -
Angewandte Chemie (International Ed. in... May 2021The m-pyridine urea (mPU) oligomer was constructed by using the intramolecular hydrogen bond formed by the pyridine nitrogen atom and the NH of urea and the...
The m-pyridine urea (mPU) oligomer was constructed by using the intramolecular hydrogen bond formed by the pyridine nitrogen atom and the NH of urea and the intermolecular hydrogen bond of the terminal carbonyl group and the NH of urea. Due to the synergistic effect of hydrogen bonds, mPU oligomer folds and exhibits strong self-assembly behaviour. Affected by folding, mPU oligomer generates a twisted plane, and one of its important features is that the carbonyl group of the urea group orientates outwards from the twisted plane, while the NHs tend to direct inward. This feature is beneficial to NH attraction for electron-rich species. Among them, the trimer self-assembles into helical nanotubes, and can efficiently transport chloride ions. This study provides a novel and efficient strategy for constructing self-assembled biomimetic materials for electron-rich species transmission.
Topics: Biomimetic Materials; Chloride Channels; Particle Size; Pyridines; Surface Properties; Urea
PubMed: 33624345
DOI: 10.1002/anie.202102174 -
Environmental Science and Pollution... Nov 2017Biodegradation of pyridine and quinoline is initiated with mono-oxygenation reactions that require an intracellular electron donor. Simultaneous biodegradation of both...
Biodegradation of pyridine and quinoline is initiated with mono-oxygenation reactions that require an intracellular electron donor. Simultaneous biodegradation of both substrates should set up competition for the intracellular electron donor that may inhibit one or more of the mono-oxygenation steps. An internal circulation baffled biofilm reactor (ICBBR) was used to evaluate the impacts of competition during pyridine and quinoline biodegradation. Compared with independent biodegradation, pyridine and quinoline removal rates were slowed when biodegraded simultaneously, although the pyridine removal rate decreased more than for quinoline. The first mono-oxygenation of quinoline (to 2-hydroxyquinoline) always was faster than the first mono-oxygenation of pyridine (to 2-hydroxypyridine), and the difference was accentuated with pyridine and quinoline which were biodegraded simultaneously due to the competition for intracellular electron donor. Competition also existed between the second mono-oxygenations, and the removal rate of 2-hydroxypyridine was faster than the rate for 2-hydroxyquinoline, even though the rate was faster for quinoline than pyridine. Adding an exogenous electron donor accelerated all mono-oxygenations in proportion to the amount of donor added, but the increments were greater for quinoline due to its higher affinity for intracellular electron donors than pyridine. When actual coking wastewater was used as the background matrix, removals of pyridine and quinoline exhibited the same competitive trends.
Topics: Biodegradation, Environmental; Biofilms; Bioreactors; Electrons; Pyridines; Quinolines
PubMed: 28921046
DOI: 10.1007/s11356-017-0082-3 -
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 -
Inorganic Chemistry Feb 2019Ruthenium(II) polypyridine complexes are one of the most extensively studied and developed systems in the family of luminescent transition-metal complexes. Notably,... (Review)
Review
Ruthenium(II) polypyridine complexes are one of the most extensively studied and developed systems in the family of luminescent transition-metal complexes. Notably, there has been a large amount of interest in the biological applications of these luminescent ruthenium(II) complexes because of their rich photophysical and photochemical properties. In this Viewpoint, we explore past and recent works on the possible biological and cellular applications of these promising complexes, with a focus on their use as bioimaging reagents, biomolecular probes, and phototherapeutic agents.
Topics: Coordination Complexes; Humans; Luminescent Agents; Molecular Imaging; Photochemotherapy; Pyridines; Ruthenium
PubMed: 30693762
DOI: 10.1021/acs.inorgchem.8b02979 -
Journal of Environmental Sciences... May 2018Simultaneous pyridine biodegradation and nitrogen removal were successfully achieved in a sequencing batch reactor (SBR) based on aerobic granules. In a typical SBR...
Simultaneous pyridine biodegradation and nitrogen removal were successfully achieved in a sequencing batch reactor (SBR) based on aerobic granules. In a typical SBR cycle, nitritation occurred obviously after the majority of pyridine was removed, while denitrification occurred at early stage of the cycle when oxygen consumption was aggravated. The effect of several key operation parameters, i.e., air flow rate, influent NH-N concentration, influent pH and pyridine concentration, on nitritation, pyridine degradation and total nitrogen (TN) removal, was systematically investigated. The results indicated that high air flow rate had a positive effect on both pyridine degradation and nitritation but a negative impact of overhigh air flow rate. With the increase of NH dosage, both nitritation and TN removal could be severely inhibited. Slightly alkaline condition, i.e., pH7.0-8.0, was beneficial for both pyridine degradation and nitritation. High pyridine dosage often resulted in the delay of both pyridine degradation and nitritation. Besides, extracellular polymeric substances production was affected by air flow rate, NH dosage, pyridine dosage and pH. In addition, high-throughput sequencing analysis demonstrated that Bdellovibrio and Paracoccus were the dominant species in the aerobic granulation system. Coexistence of pyridine degrader, nitrification related species, denitrification related species, polymeric substances producer and self-aggregation related species was also confirmed by high-throughput sequencing.
Topics: Biodegradation, Environmental; Bioreactors; Denitrification; Nitrification; Nitrogen; Pyridines; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical
PubMed: 29778165
DOI: 10.1016/j.jes.2017.09.016