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Analytical and Bioanalytical Chemistry Jul 2021Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site...
Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories is important for drug enforcement agencies and the forensic community in general. However, detecting methamphetamine in the presence of nicotine and cigarette smoke by ion mobility spectrometry faces difficulty due to the overlapped spectral peaks of methamphetamine and nicotine. In this work, a new method was developed to detect MA using pyridine as a dopant in the presence of nicotine by a homemade ion mobility spectrometry. The reduced mobilities of MA and nicotine were measured under the temperatures of the drift tube from 40 to 120 °C and doping with pyridine. The result shows that the temperature of 100 °C is beneficial to resolve the two substances. The concentration of doped pyridine is optimized to be 18 ppm. In this doped experiment, the reaction rate of nicotine is higher than that of MA by measuring the instrumental responses of MA and nicotine. No matter how high the nicotine content is, the interference of nicotine can be eliminated in the detection of MA doped with pyridine. This method is also successfully applied for the determination of MA and nicotine simultaneously in real saliva samples. The limit of detection of MA was measured to be about 0.5 ng/μL. The promising results in this work provide an effective method for on-site detection of MA.
Topics: Central Nervous System Stimulants; Humans; Illicit Drugs; Ion Mobility Spectrometry; Limit of Detection; Methamphetamine; Nicotine; Pyridines; Saliva; Substance Abuse Detection
PubMed: 33948704
DOI: 10.1007/s00216-021-03370-z -
Inorganic Chemistry Jun 2022As an element-equivalent theranostic pair, lead-203 (Pb, 100% EC, half-life = 51.92 h) and lead-212 (Pb, 100% β, half-life = 10.64 h), through the emission of γ rays...
As an element-equivalent theranostic pair, lead-203 (Pb, 100% EC, half-life = 51.92 h) and lead-212 (Pb, 100% β, half-life = 10.64 h), through the emission of γ rays and an α particle in its decay chain, respectively, can aid in the development of personalized targeted radionuclide treatment for advanced and currently untreatable cancers. With these isotopes currently being used in clinical trials, an understanding of the relationship between the chelator structure, ability to incorporate the radiometal, and metal-complex stability is needed to help design appropriate chelators for clinical use. Herein, we report an investigation into the effect of ring size in macrocyclic chelators where pyridine, an intermediate Lewis base, acts as an electron donor toward lead. Crown-4Py (4,7,13,16-tetrakis(pyridin-2-ylmethyl)-1,10-dioxa-4,7,13,16-tetraazacyclooctadecane), cyclen-4Py (1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane), and NOON-2Py (7,16-bis(pyridin-2-ylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane) were synthesized and analyzed for their ability to coordinate Pb. Metal complex stability was investigated via [Pb]Pb radiolabeling studies, H NMR spectroscopy, X-ray crystallography, and potentiometry. With the smallest macrocyclic backbone, cyclen-4Py had the highest radiochemical yield, while, in descending order, crown-4Py and NOON-2Py had the lowest. Thermodynamic stability constants (log ) of 19.95(3), 13.29(5), and 11.67 for [Pb(Cyclen-4Py)], [Pb(Crown-4Py)], and [Pb(NOON-2Py)], respectively, correlated with their radiochemical yields. The X-ray crystal structure of the least stable complexes [Pb(NOON-2Py)] revealed a hemidirected Pb center, as reflected by a void within the coordination sphere, and [Pb(Crown-4Py)] showed an average Pb-N pyridine interatomic distance of >3 Å. By contrast, the crystal structure of [Pb(Cyclen-4Py)] showed shorter Pb-N pyridine interactions, and in solution, only one highly symmetric isomer existed for this complex, whereas conformational flexibility was observed for both [Pb(Crown-4Py)] and [Pb(NOON-2Py)] at the NMR timescale. This study illustrates the importance of the macrocyclic backbone size when incorporating bulky electron-donor groups into the design of a macrocyclic chelator as it affects the accessibility of lead to the donor arms. Our results show that cyclen-4Py is a promising chelator for future studies with this theranostic pair.
Topics: Chelating Agents; Coordination Complexes; Crystallography, X-Ray; Cyclams; Lead; Ligands; Pyridines
PubMed: 35704752
DOI: 10.1021/acs.inorgchem.2c01114 -
Journal of Biological Inorganic... Aug 2021Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where...
Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity.
Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (10 and 10 M) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied.
Topics: Antineoplastic Agents; Cell Proliferation; Cells, Cultured; Coordination Complexes; DNA; Drug Screening Assays, Antitumor; Humans; Kinetics; Molecular Docking Simulation; Palladium; Platinum; Pyridines; Serum Albumin, Human
PubMed: 34268603
DOI: 10.1007/s00775-021-01879-3 -
Future Medicinal Chemistry Jun 2023Due to the close relationship of diabetes with hypertension reported in various research, a set of pyridine derivatives with US FDA-approved drug cores were designed...
Due to the close relationship of diabetes with hypertension reported in various research, a set of pyridine derivatives with US FDA-approved drug cores were designed and integrated by artificial intelligence. Novel pyridines were designed and synthesized. Compounds - were evaluated for their structure and were screened for their antidiabetic (α-amylase) activity and anticancer (HepG2) activity by methyl thiazolyl tetrazolium assay. Comparative 3D quantitative structure-activity relationship analysis and pharmacophore generation were carried out. The study revealed and as good alternatives to acarbose as antidiabetic agents, and as a more viable, better alternative to doxorubicin in the methyl thiazolyl tetrazolium assay. This combination of studies identifies new and more active analogs of existing FDA-approved drugs for the treatment of diabetes.
Topics: Hypoglycemic Agents; Molecular Docking Simulation; Artificial Intelligence; Pyridines; Structure-Activity Relationship; Molecular Structure
PubMed: 37503685
DOI: 10.4155/fmc-2023-0132 -
International Journal of Molecular... Apr 2023About twenty molecules sharing 1-chromeno[3,2-]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl...
About twenty molecules sharing 1-chromeno[3,2-]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-]pyridin-10-ones (1,2,3,4-THCP-10-ones, ) or 2,3-dihydro-2-methyl-1-chromeno[3,2-]pyridines (2,3-DHPCs, ). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives inhibit MAO A (IC about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one , bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC 0.51 μM) and moderate inhibitor of both ChEs (ICs 7-8 μM); (iii) the 1-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog achieving MAO B IC of 3.51 μM. The MAO B inhibitor deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson's disease and neuroprotectant for Alzheimer's disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog exerts anti-tumor activity with ICs in the range 4.83-11.3 μM.
Topics: Humans; Monoamine Oxidase Inhibitors; Structure-Activity Relationship; Monoamine Oxidase; Pyridines; Cholinesterase Inhibitors
PubMed: 37175433
DOI: 10.3390/ijms24097724 -
Anti-cancer Agents in Medicinal... 2022Despite emerging research on new treatment strategies, chemotherapy remains one of the most important therapeutic modalities for cancers. Imidazopyridines are important...
BACKGROUND
Despite emerging research on new treatment strategies, chemotherapy remains one of the most important therapeutic modalities for cancers. Imidazopyridines are important targets in organic chemistry and, given their numerous applications, they are worthy of attention.
OBJECTIVE
The objective of this study was to design and synthesize a novel series of imidazo[1,2-a]pyridine-derived compounds and investigate their antitumor effects and the underlying mechanisms.
METHODS
Imidazo[1,2-a]pyridine-derived compounds were synthesized with new strategies and conventional methods. The antitumor activities of the new compounds were evaluated by MTT assay. Flow cytometry and immunofluorescence were performed to examine the effects of the most effective antiproliferative compound on cell apoptosis. Western blot analysis was used to assess the expression of apoptotic proteins.
RESULTS
Fifty-two new imidazo[1,2-a]pyridine compounds were designed and successfully synthesized. The compound, 1-(imidazo[1,2-a]pyridin-3-yl)-2-(naphthalen-2-yl)ethane-1,2-dione, named La23, showed high potential for suppressing the viability of HeLa cells (IC50 15.32 μM). La23 inhibited cell proliferation by inducing cell apoptosis, and it reduced the mitochondrial membrane potential of HeLa cells. Moreover, treatment with La23 appeared to increase the expression of apoptotic-related protein P53, Bax, cleaved caspase-3, and cytochrome c at a low concentration range.
CONCLUSION
The novel imidazo[1,2-a]pyridine compound, La23, was synthesized and it suppressed cell growth by inducing cell apoptosis via the p53/Bax mitochondrial apoptotic pathway.
Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Cell Survival; HeLa Cells; Humans; Membrane Potential, Mitochondrial; Pyridines; Tumor Suppressor Protein p53; bcl-2-Associated X Protein
PubMed: 34353269
DOI: 10.2174/1871520621666210805130925 -
European Journal of Medicinal Chemistry Feb 2020A new class of 2-amino-4-(1,2,4-triazol)pyridine derivatives were designed and synthesized as potent epidermal growth factor receptor inhibitors. In particular, compound... (Review)
Review
A new class of 2-amino-4-(1,2,4-triazol)pyridine derivatives were designed and synthesized as potent epidermal growth factor receptor inhibitors. In particular, compound 10c exhibited significant inhibitory against EGFR, and also displayed potent anti-proliferative activity against non-small cell lung cancer cell line H1975. Besides, compound 10j showed potent inhibitory activity against glioblastoma cell line U87-EGFRvⅢ, which was at least 3-fold more potent than Osimertinib and 25-fold superior to Lazertinib. Moreover, molecular modeling and molecular dynamics simulations disclosed the binding model of the most active compound to the domain of EGFR. This contribution provides 2-amino-4-(1,2,4-triazol)pyridines as a new scaffold for EGFR and/or EGFRvⅢ inhibitor.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Design; ErbB Receptors; Humans; Protein Kinase Inhibitors; Pyridines
PubMed: 31869655
DOI: 10.1016/j.ejmech.2019.111966 -
Bioresource Technology Sep 2023Some industrial wastewaters contain high amounts of toxic nitrogen-containing heterocyclic compounds, which may inhibit the efficiency of biological treatment. This work...
Some industrial wastewaters contain high amounts of toxic nitrogen-containing heterocyclic compounds, which may inhibit the efficiency of biological treatment. This work systematically investigated how exogenous pyridine affected the anaerobic ammonia oxidation (anammox) system and discussed the microscopic response mechanisms based on genes and enzymes. The anammox efficiency was not seriously inhibited by pyridine less than 50 mg/L. Bacteria secreted more extracellular polymeric substances to resist pyridine stress. After 6 days stress with 80 mg/L pyridine, the nitrogen removal rate of anammox system lost 47.7%. Long-term stress of pyridine reduced anammox bacteria by 7.26% and the expression of functional genes by 45%. Pyridine could actively bind to hydrazine synthase and ammonium transporter. This work fills a research gap in the ongoing threat of pyridines to anammox, and has guiding value for the application of anammox process in the treatment of ammonia-rich wastewater containing pyridine.
Topics: Anaerobic Ammonia Oxidation; Bioreactors; Oxidation-Reduction; Ammonium Compounds; Wastewater; Bacteria; Pyridines; Nitrogen; Denitrification; Sewage
PubMed: 37290710
DOI: 10.1016/j.biortech.2023.129273 -
Bioorganic Chemistry Jul 2020SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which affects the transduction of multiple signaling pathways, including RAS-ERK,...
SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which affects the transduction of multiple signaling pathways, including RAS-ERK, PI3K-AKT and JAK-STAT. SHP2 also plays an important role in the programmed cell death pathway (PD-1/PD-L1). Studies have shown that SHP2 is associated with a variety of cancers, including breast, liver and gastric cancers. Therefore, the development of SHP2 inhibitors has attracted extensive attention. In this study, based on the known inhibitor 1 (SHP099), novel SHP2 inhibitors were designed by means of scaffold hopping, and 35 pyridine derivatives as SHP2 inhibitors were found. The in vitro enzyme activity assay was performed on these compounds, and multiple selective SHP2 inhibitors with activity potency similar to that of SHP099 were obtained. Among them, compound (2-(4-(aminomethyl)piperidin-1-yl)-5-(2,3-dichlorophenyl)pyridin-3-yl)methanol (11a) was the most potent and highly selective SHP2 inhibitor with an in vitro enzyme activity IC value of 1.36 μM. Fluorescence titration assay verified that 11a bound directly to SHP2 protein. Subsequently, cell assay of representative compounds showed that these compounds could effectively inhibit the proliferation of Ba/F cells. In addition, the pharmacokinetic characteristics of the designed compounds were analyzed by the in silico ADMET prediction. Molecular docking study provided more detailed information on the binding mode of compounds and SHP2 protein. In brief, this study reported for the first time that pyridine derivatives as novel SHP2 inhibitors had good inhibitory activity and selectivity, providing new clues for the development of small molecule SHP2 inhibitors.
Topics: Animals; Cell Line; Cell Proliferation; Drug Design; Enzyme Inhibitors; Humans; Mice; Models, Biological; Molecular Docking Simulation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Pyridines
PubMed: 32380342
DOI: 10.1016/j.bioorg.2020.103875 -
Molecular Diversity Apr 2022Magnetite nanoparticles (MNPs) composed of γ-FeO and hydroxyapatite (HAp) were modified by hexamethylen-1,6-diisocyanate (HMDI) followed by thiourea dioxide and used as...
Magnetite nanoparticles (MNPs) composed of γ-FeO and hydroxyapatite (HAp) were modified by hexamethylen-1,6-diisocyanate (HMDI) followed by thiourea dioxide and used as recyclable catalyst for the synthesis of some newly derivatives of chromeno[2,3-b]pyridine. The products were synthesized in excellent yields via one-pot three-component reactions of 3-cyano-6-hydroxy-4-methyl-pyridin-2(1H)-one with aldehydes and dimedone under solvent-free conditions. The successful synthesis of products were confirmed using Fourier transform infrared (FTIR), proton/carbon nuclear magnetic resonance (H/C NMR), and mass spectroscopies as well as physical data (e.g., melting points and elemental composition). The in vitro antioxidant and antifungal activities of the synthesized samples were evaluated using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and potato dextrose agar (PDA) medium, respectively. Based on results, the chromeno[2,3-b]pyridine derivatives exhibited excellent biological activities that qualified them for biomedical applications.
Topics: Antioxidants; Catalysis; Magnetite Nanoparticles; Pyridines; Solvents
PubMed: 33861411
DOI: 10.1007/s11030-021-10201-x