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Journal of Insect Physiology Apr 2017Age estimation of adult flies could extend the possible window of time for calculating the minimal postmortem interval (PMI) by means of entomological methods....
Age estimation of adult flies could extend the possible window of time for calculating the minimal postmortem interval (PMI) by means of entomological methods. Currently, this is done by estimating the time required by necrophagous Diptera to reach certain juvenile developmental landmarks, and the method only works until the end of metamorphosis and emergence of the adult fly. Particularly at indoor crime scenes, being able to estimate the age of trapped adult flies would be an important tool with which to extend the calculable PMI beyond the developmental period. Recently, several promising age-dependent morphological and physiological characteristics of adult insects have been investigated in medical and forensic entomology, but the results are still preliminary and restricted to a few species. We examined adults of the forensically relevant blow fly species Calliphora vicina and investigated the fluorescence levels of pteridine, a group of metabolites that accumulates in the eyes during aging. From Day 1 to Day 25 post-emergence, flies were kept at three different temperature regimes (20°C, 25°C, and fluctuating temperatures in the context of a field study) and 12:12 L:D. From Day 1 until Day 7, the fluorescence of pteridine was determined on a daily basis, and thereafter, every three days. The achieved fly age was multiplied with the relevant temperature and converted into accumulated degree-days (ADD). The fluorescence level of pteridine increased linear with increasing ADD (females: R=0.777; males: R=0.802). The difference between sexes was significant (p<0.001). Neither head weight nor temperature had an effect on pteridine fluorescence. Because the variation in pteridine fluorescence increased with increasing ADD, it seems favorable to combine several aging methods for more precise results. In context, we emphasize that different body parts of the same specimen can be used to analyze cuticular hydrocarbons (legs), pteridine fluorescence (head/eyes), and gonotrophic stage (female abdomen).
Topics: Aging; Animals; Diptera; Entomology; Female; Fluorescence; Forensic Sciences; Male; Pteridines
PubMed: 28267461
DOI: 10.1016/j.jinsphys.2017.03.002 -
Marine Drugs Feb 2021Two new fluorescent pteridine alkaloids, tedaniophorbasins A () and B (), together with the known alkaloid -methyltryptamine, were isolated, through application of mass...
Two new fluorescent pteridine alkaloids, tedaniophorbasins A () and B (), together with the known alkaloid -methyltryptamine, were isolated, through application of mass directed purification, from the sponge collected from northern New South Wales, Australia. The structures of tedaniophorbasins A and B were deduced from the analysis of 1D/2D NMR and MS data and through application of C NMR DFT calculations. Tedaniophorbasin A possesses a novel 2-imino-1,3-dimethyl-2,3,7,8-tetrahydro-1H-[1,4]thiazino[3,2-g]pteridin-4(6)-one skeleton, while tedaniophorbasin B is its 2-oxo derivative. The compounds show significant Stokes shifts (~14,000 cm) between excitation and emission wavelengths in their fluorescence spectra. The new compounds were tested for bioactivity against chloroquine-sensitive and chloroquine-resistant strains of the malaria parasite , breast and pancreatic cancer cell lines, and the protozoan parasite but were inactive against all targets at 40 µM.
Topics: Alkaloids; Animals; Antineoplastic Agents; Cell Line, Tumor; Humans; Magnetic Resonance Spectroscopy; Plasmodium falciparum; Porifera; Pteridines; Trypanosoma brucei brucei
PubMed: 33562248
DOI: 10.3390/md19020095 -
Organic & Biomolecular Chemistry Feb 2020Computed association strengths for 43 purine and pteridine quartets (38 to 100 kcal mol) show excellent linear correlation with π-conjugation gain in the assembled...
Computed association strengths for 43 purine and pteridine quartets (38 to 100 kcal mol) show excellent linear correlation with π-conjugation gain in the assembled monomers (r = 0.965). Even quartets having the same secondary electrostatic interactions can display very different association strengths depending on the π-conjugation patterns of the monomeric units.
Topics: Density Functional Theory; Hydrogen Bonding; Molecular Structure; Pteridines; Purines; Static Electricity
PubMed: 31967161
DOI: 10.1039/c9ob02412c -
Archives of Biochemistry and Biophysics Oct 1966
Topics: Azotobacter; Bacteria; Chromatium; Chromatography, Paper; Escherichia coli; Photosynthesis; Pteridines; Rhodopseudomonas; Rhodospirillum
PubMed: 5339537
DOI: 10.1016/0003-9861(66)90124-x -
Future Medicinal Chemistry 2015Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of...
BACKGROUND
Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.
RESULTS
A novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).
CONCLUSION
The 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.
Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Colitis; Diamines; Disease Models, Animal; Edema; Free Radical Scavengers; Lipoxygenase; Lipoxygenase Inhibitors; Male; Molecular Docking Simulation; Protein Binding; Protein Structure, Tertiary; Pteridines; Rats; Reactive Oxygen Species; Glycine max
PubMed: 26423719
DOI: 10.4155/fmc.15.104 -
Nature Communications Oct 2014The use of biologically occurring redox centres holds a great potential in designing sustainable energy storage systems. Yet, to become practically feasible, it is...
The use of biologically occurring redox centres holds a great potential in designing sustainable energy storage systems. Yet, to become practically feasible, it is critical to explore optimization strategies of biological redox compounds, along with in-depth studies regarding their underlying energy storage mechanisms. Here we report a molecular simplification strategy to tailor the redox unit of pteridine derivatives, which are essential components of ubiquitous electron transfer proteins in nature. We first apply pteridine systems of alloxazinic structure in lithium/sodium rechargeable batteries and unveil their reversible tautomerism during energy storage. Through the molecular tailoring, the pteridine electrodes can show outstanding performance, delivering 533 Wh kg(-1) within 1 h and 348 Wh kg(-1) within 1 min, as well as high cyclability retaining 96% of the initial capacity after 500 cycles at 10 A g(-1). Our strategy combined with experimental and theoretical studies suggests guidance for the rational design of organic redox centres.
Topics: Bioelectric Energy Sources; Electrodes; Flavins; Lithium; Oxidation-Reduction; Pteridines; Sodium
PubMed: 25359101
DOI: 10.1038/ncomms6335 -
Medicinal Research Reviews Sep 2004Inhibitors of the family of nitric oxide synthases (NOS-I-III; EC 1.14.13.39) are of interest as pharmacological agents to modulate pathologically high nitric oxide (NO)... (Review)
Review
Inhibitors of the family of nitric oxide synthases (NOS-I-III; EC 1.14.13.39) are of interest as pharmacological agents to modulate pathologically high nitric oxide (NO) levels in inflammation, sepsis, and stroke. In this article, we discuss the approach for targeting the unique (6R)-5,6,7,8-tetrahydro-L-biopterin (H4Bip) binding site of NOS by appropriate inhibitors. This binding site maximally increases enzyme activity and NO production from the substrate L-arginine upon cofactor binding. The first generation of H4Bip-based NOS inhibitors was based on 4-amino H4Bip derivatives in analogy to anti-folates such as methotrexate. In addition, we discuss the structure-activity relationship of a related series of 4-oxo-pteridine derivatives. Furthermore, molecular modeling studies provide an understanding of pterin antagonism on a structural level based on favorable and unfavorable interactions between protein binding site and ligands. These techniques include 3D-QSAR (CoMFA, CoMSIA) to understand ligand affinity and GRID/consensus principal component analysis (CPCA) to learn about selectivity requirements. Collectively these approaches, in combination with the presented SAR and structural data, provide useful information for the design of novel NOS inhibitors with increased isoform selectivity.
Topics: Animals; Arginine; Binding Sites; Biopterins; Brain Ischemia; Enzyme Inhibitors; Humans; Inflammation; Isoenzymes; Neurodegenerative Diseases; Nitric Oxide Synthase; Protein Conformation; Pteridines; Quantitative Structure-Activity Relationship; Sepsis; Structure-Activity Relationship
PubMed: 15224385
DOI: 10.1002/med.20005 -
Talanta Oct 2014Pteridinic derivatives are important biomolecules considered as biomarkers for several diseases, especially in cancer and infectious pathologies. A new fluorimetric-HPLC...
Pteridinic derivatives are important biomolecules considered as biomarkers for several diseases, especially in cancer and infectious pathologies. A new fluorimetric-HPLC method for the analysis of nine pteridines in human serum has been reported. Two analytical columns composed by C18 porous and fused core particles were assayed and the results compared. Fused core particle column allows us adequate separation, in only one run and in 15 min. Acid precipitation step of the proteins and clean-up process with an Isolute ENV+ (hydroxylated polystyrene-divinylbenzene copolymer) cartridge of the serum samples have been optimized. Analytes were determined by fluorimetric detection, exciting at 272 nm and measuring the fluorescence emission at 410 nm for isoxanthopterin, at 465 nm for xanthopterin, and at 445 nm for the analysis of the other pteridines. Detection limits between 0.07 and 0.61 ng mL(-1) were calculated according to Clayton criterium. Intraday precision varied from 1.2 to 5.3 and interday precision between 1.2 and 7.4, both expressed as RSD (%). External standard and standard addition calibrations were compared in the analysis of serum samples. The pteridine amounts in serum (expressed as ng mL(-1) ± confidence interval) were 3.69 ± 1.78; 1.35 ± 0.24; 0.46 ± 0.14; 0.54 ± 0.24; 0.84 ± 0.55; 2.10 ± 0.51 and 0.23 ± 0.11 for XAN, NEO, MON, ISO, BIO and 6HMPT, respectively, using the external standard method. Comparable results were obtained by the standard addition method. It is noticeable that 7BIO was not detected in the healthy serum samples analyzed.
Topics: Adolescent; Adult; Aged; Biomarkers; Calibration; Child; Child, Preschool; Chromatography, High Pressure Liquid; Fluorometry; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Middle Aged; Pteridines; Reference Values; Reproducibility of Results; Young Adult
PubMed: 25059167
DOI: 10.1016/j.talanta.2014.04.052 -
Bioorganic & Medicinal Chemistry Jul 2019Recently, diverse kinase inhibitors were reported having interaction with BRD4. It provided a strategy for developing a new structural framework for the next-generation...
Recently, diverse kinase inhibitors were reported having interaction with BRD4. It provided a strategy for developing a new structural framework for the next-generation BRD4-selective inhibitors. Starting from PLK1 kinase inhibitor BI-2536, we designed 18 compounds by modifying dihydropteridine core. Compound 23 showed potent BRD4 inhibitory activities with IC of 79 nM and no inhibitory activities for PLK1. Cell antiproliferation assay was performed and potent inhibitory activity against MV4;11 with IC of 1.53 μM. Cell apoptosis and western blotting indicated compound 23 induced apoptosis by down-regulating c-Myc. These novel selective BRD4 inhibitors provided new lead compounds for further drug development.
Topics: Cell Cycle Proteins; Humans; Molecular Structure; Pteridines; Transcription Factors
PubMed: 31079968
DOI: 10.1016/j.bmc.2019.05.006 -
European Journal of Medicinal Chemistry Apr 2020Protein kinase inhibitors and epigenetic regulatory molecules are two main kinds of anticancer drugs developed in recent years. Both kinds of drugs harbor their own...
Protein kinase inhibitors and epigenetic regulatory molecules are two main kinds of anticancer drugs developed in recent years. Both kinds of drugs harbor their own advantages and disadvantages in the treatment of cancer, and the development of small molecules which could target at kinases and epigenetic targets simultaneously can avoid the defects of drugs which only targets at kinases or epigenetic proteins. In this study, a series of 4,5-dihydro-[1,2,4]triazolo [4,3-f]pteridine derivatives were designed and synthesized based on the structure of PLK1 inhibitor BI-2536. Subsequent targets affinity screen and antiproliferative activity test led to the discovery of the most potent dual PLK1/BRD4 inhibitor 9b with good potency for both PLK1 (IC = 22 nM) and BRD4 (IC = 109 nM) as well as favorable antiproliferative activity against a panel of cancer cell lines. 9b could induce cell cycle arrest and apoptosis in acute myeloid leukemia cell line MV 4-11 in a concentration dependent manner. It could also downregulate the transcription of several proliferation-related oncogenes, including c-MYC, MYCN and BCL-2. Finally, in a MV4-11 mouse xenograft model, 9b exhibited favorable in vivo antitumor activity with 66% tumor growth inhibition (TGI) at a dose of 60 mg/kg while without obvious toxicity. This study thus provided us a start point for the development of new dual PLK1/BRD4 inhibitors as anticancer agents.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Male; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Structure; Neoplasms, Experimental; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Pteridines; Structure-Activity Relationship; Transcription Factors; Triazoles; Tumor Cells, Cultured; Polo-Like Kinase 1
PubMed: 32088495
DOI: 10.1016/j.ejmech.2020.112152