furans

..The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery...

..Through the identification of a new mechanism of action for RITA, our study uncovers a novel link between the DNA damage response-p53 pathway and the protein translational machinery...

..These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53...

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..This review will highlight recent findings in the research into molecules capable of modulating p53 protein activities and mechanisms that activate the p53 pathway, restoring response to therapy in haematological malignancies...

..Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment...

..7. These results would suggest that YC-1 activates sGC of human platelets by a NO-dependent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway...

..These data indicate that strategies of p53 reactivation by MDM2 inhibition should also take into consideration MDM2 targets other than p53, such as the apoptosis activator HIPK2...

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..Our results show the activity of reversed diamidines against T. cruzi and suggested that the compounds merit in vivo studies...

..The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity...

..These findings may have important implications for the rational design of effective rectal microbicides...

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..Our results support the therapeutic potential for PI3 kinase inhibitors with a PI-103-like profile as therapeutic agents for the treatment of glioma...

..These data certainly makes an argument for investigating unexpected effects of rational drug combinations on immunocompetent animal models prior to conducting clinical studies...

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..In conclusion, DB868 with oral and DB829 with parenteral application are potential candidates for further development of a second-stage African sleeping sickness drug...

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..Inhibition of oncogenes by p53 reduces the cell's ability to buffer proapoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression...

..Among these metabolites, 1-4 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 3,14-ether linkage. In addition, 5 is the first secocembrane possessing two tetrahydrofuran moieties with 3,14- and 4,7-ether linkages...

..These results give new insights into the mechanism of action of these potent neurotoxic molecules...

..Thus, RITA is a promising lead for the development of anti-cancer drugs that reactivate the tumor suppressor function of p53 in cancer cells irrespective whether they express mutant or wild type p53...

..These results suggest that squamocin is a potentially promising anticancer compound...

..We also observed that PTX-2-induced cell cycle arrest was not restricted to p53 status in human breast cancer cells...

..Therefore, these results suggest that Bim-mediated apoptosis following actin damage due to deregulation of Cdk2 and the cell cycle by the absence of functional p53...

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..1% UC781 formulation. These results provide additional support for the continued development of UC781 formulations as anti-HIV microbicides...

..These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent...

..Therefore, these results suggest that Bim triggers apoptosis by activating Bax in p53-deficient tumors upon actin damage, and that actin inhibitors may be potent chemotherapeutic agents against p53-deficient tumors...

..Acceptability research is essential in early phases of microbicide development to identify potential problems, understand user preferences, and introduce changes if needed...

..Ovulation is resumed shortly after stopping treatment, and a normal menses occurs after the first progesterone peak. Both compounds may be interesting options for the prevention and treatment of breast cancer and for fertility control...

..Our results suggest that inotilone may have potential to be developed into an effective anti-inflammatory agent...

..The importance of finding effective antidiabetic therapeutics led us to further investigate natural compounds...

..The purpose of this study was to determine whether inhibition of PI3K, a downstream molecule of both EGFR and MET, could overcome HGF-mediated EGFR-TKI resistance in EGFR mutant lung cancer cells PC-9 and HCC827...

..These molecular mechanisms provide that PTX-2 induces G2/M phase arrest, endoreduplication, and apoptosis through the ERK and JNK signal pathway via actin depolymerization...

..Formulation of solid dispersions did however not further improve the drug dissolution rate compared to that of physical mixtures. Nonetheless, variability of dissolution results was considerably reduced upon solid dispersion formulation...

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..We concluded that PTX-2 suppressed telomerase activity through the transcriptional and post-translational suppression of hTERT and this process precedes cellular differentiation of human leukemia cells...

..Density functional theory calculations and application to a short route to thunberginol A were also described. [reaction: see text]...

..Taken together, these results suggest that anti-cancer activities induced by PTX-2 may be mediated in part through suppression of constitutive NF-kappaB activity...

..Examination of the PTX-binding site on actin provides a rationalization for the structure-activity relationships observed in vivo and in vitro, and may provide a basis for predicting toxicity of PTX analogues...

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..Therefore, we conclude that cytoskeletal disruption is a key mechanism of PTX6-induced toxicity in eukaryotic cells...

..In both AML and CLL cells exposure to RITA resulted in induction of intracellular p53. We conclude that small molecules targeting p53 might be of clinical importance in the future for treating drug-resistant leukaemia...

..Biological studies revealed that compound 7 exhibited cytotoxic activity against COLO-250 and KB-16 cells, and compound 1 is active against KB-16 cells...

..The European Food Safety Authority's (EFSA) Scientific Panel on Contaminants in the Food Chain (CONTAM) recommended these studies as part of a reliable risk assessment of furan in food...

..As this may give rise for concern, in this review, the currently available toxicological and mechanistic data of furan are summarized and discussed with regard to its applicability in assessing the risk of furan in human diet...

..7 microM. Compounds 3-8 were isolated from the title plant for the first time...

..Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza...

..Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes...

..It also induced Bax expression, enhanced caspase-3 activity, and caused apoptotic cell death in T24 cells. In summary, these results suggest that annonacin is potentially a promising anti-cancer compound...

..These results suggest that arctigenin exerted significant neuroprotective effects on glutamate-injured primary cultures of rat cortical cells by directly binding to kainic acid receptors and partly scavenging of free radicals...

..These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G(2) and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line...

..Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors...

..Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging...

..Our studies reveal that in uninduced E.coli the effects of individual polymerases in the replication of plasmids containing F or AP are distinct. However, when cells are SOS-induced, the biological effects of F and AP are similar...

..Oligonucleotide purity is assayed using the DNA repair enzyme formamidopyrimidine DNA glycosylase and by ESI-MS...

..Endo IV incises Fapy.dG to less than 5% under comparable reaction conditions, suggesting that the lesion exists almost exclusively as its beta-anomer in DNA...

..The similar effects of Fapy.dG and 8-oxodG on DNA polymerase and repair enzymes in vitro raise the question as to whether Fapy.dG elicits similar effects in vivo...

..Novel findings have indicated the possibility that the unique modulating activity profiles of the EGb 761 (definition see editorial) constituents examined are due to their effects on the anion homeostasis of central neurons...

..The present study determines the contributions to toxicity equivalence (TEQ) from polychlorinated dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) using butter samples from 24 countries world wide...

..We thus conclude that the picrotoxin-specific effects on the M2-M3 loop are mediated allosterically. This suggests that the M2-M3 loop responds differently to the occupation of different binding sites...

..The mechanism of action of beta-aminosquamocin 2, against these two respiratory targets, is studied and discussed in view of current structure-activity relationship knowledge in the acetogenin series...

..Squamoquinone, tenfold more potent than squamocin as an inducer of apoptosis, emerged as a promising compound, as it induces apoptosis through a mitochondrial caspase-dependent pathway...

..This review covers the design, synthesis, and biological evaluation of acetogenin analogues...

Dicationic 2,5-bis(4-guanidinophenyl)furans 5a-5f, 2,5-bis[4-(arylimino)aminophenyl]furans 6a-6b and 6e-6k, and 2,5-bis[4-(alkylimino)aminophenyl]furans 6c-6d have been synthesized starting from 2,5-bis[tri-n-butylstannyl]furan...

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..Thiophene derivatives were toxic when they were present at concentrations of 0.1% or greater; however, addition of trace amounts of phenylalanine plus tyrosine greatly reduced this effect...

..The formamide was derived from a nitro group at C5. The phosphoramidite coupled in 80% yield via a single 15-min coupling using tetrazole as activator. Oligonucleotides as long as 36 nucleotides were prepared and characterized by ESI-MS...

..As multiple modes of action may apply to bilobalide, it could be useful in developing therapy for disorders involving cerebral ischemia and neurodegeneration...

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..These results indicate that Fapy-dA and Fapy-dG will be sufficiently long-lived in DNA so as to warrant investigation of their genotoxicity, and both anomers will be present during this time...

..The more abundant trans-C(8)-diol ester of okadaic acid (2) isolated from the same Dinophysis extract was rapidly hydrolyzed to okadaic acid in vitro by the supernatant from green-lipped mussel hepatopancreas...

..This review summarises the extensive work on furanones focusing on their natural and applied antifouling activities...

..Polychlorinated dibenzo-dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCBs) have been useful markers in some settings...

..The results indicate that all the studied CHFs inhibit GJIC in WB-F344 cells by altering Cx43 expression...

..RITA may serve as a lead compound for the development of an anticancer drug that targets tumors with wild-type p53...

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..These findings indicate that MX is not mutagenic, mitogenic or carcinogenic in mice, and suggest that the compound exerts epigenetic actions leading to GJIC inhibition...

..For example, some of the guanacone derivatives prepared were two orders of magnitude more potent than the parent compound for specific cell lines...

..The most abundant fatty acid esters in the fractionated sample were, in order, the 16:0, 22:6, 14:0, 16:1, 18:4, and 20:5 fatty acids, although a wide array of other PTX-2 seco acid fatty acid esters were also present at low levels...

..Conclusive toxicological studies are required to elucidate the public health relevance of the different PTXs derivatives and to provide the scientific basis for regulations...

..As neither the in vivo nor the in vitro studies disclose any significant increase in the micronucleus frequency after treatment with furan, our results support that the carcinogenicity of furan is caused by a non-genotoxic mechanism...

..These findings suggest that the THF-diols modulate hypothalamo-pituitary axis to regulate steroid hormone-dependent male sexual behavior...

..5'-TTGT. Collectively, the SPR and footprinting results show that the consensus sequence 5'-(A/T)-TG-(A/T) represents the optimal site for cooperative dimerization of the heterocyclic diamidine DB293...

..Here we show that 1 promotes germination of a number of plant species at a level similar to that observed with plant-derived smoke water...

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..2.15 cells by inducing apoptosis. Most of the bullatacin-induced cell death was found to be due to apoptosis, as determined by double staining with fluorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI)...

..This is the first report of PTX11, together with the confirmation of OA-D8 diol-ester in D. acuta populations from Europe...

..These results suggest that oral administration of bilobalide and EGb 761 protect against ischemia-induced neuron death and reductions in mitochondrial gene expression...

..It does, however, affect the architecture of the biofilm and enhances the process of bacterial detachment, leading to a loss of bacterial biomass from the substratum...

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..Therefore, we exposed animals to a mixture of dioxins, furans, and polychlorinated biphenyls (PCBs) that included TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-..

..harveyi via of autoinducer 2 (AI-2) as well as inhibited by 26-600-fold the quorum sensing of E. coli via AI-2; hence, this furanone is a non-specific intercellular signal antagonist...

..The resulting DNA strand breaks are visualized by the increase in gamma-H2AX foci and may originate micronuclei at the subsequent mitosis...

..This study evaluated the effect of a single dose and 5 additional consecutive daily doses of UC781 gel at concentrations of 0.1%, 0.25%, 1.0%, and 0% on urogenital irritation...

..To our knowledge, this is the first study in which such analyses have been applied to structural analogues for which both mutagenic potency and mutation spectra date were available...

..Unlike the other toxins, GYM was concentrated in tissues outside the digestive gland and levels did not decrease over 5 months. The depuration rates of YTX and PTXs from mussels were modelled...

..Finally, to help determine the correlation between gene expression changes and liver pathology, we applied traditional microarray visualization tools to the assessment of clinical chemistry and pathology parameters...

..there is a concern for persistent or increasing environmental levels of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated dibenzo-p-dioxins/furans (PXDD/Fs)...

..involve inter- and intramolecular reactions of iminium salts with nucleophilic partners, especially oxygenated furans; and (4) explore 1,2-metallate rearrangements as a novel entry to unsaturated nitrogen compounds...

..benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles, isoxazoles, pyrazoles, pyridines, quinolines, coumarins, indenes, indenones, ..

..chromones, benzothiophenes, benzoselenophenes, phthalides, isocoumarins, isochromenes, isoquinolines, quinolines, furans, isoxazoles and various spirotrienones...

..and intramolecular reactions of iminium salts with electron-rich nucleophilic partners, especially oxygenated furans. In the arena of total synthesis, we will: (1) continue development of intramolecular hetero Diels-Alder reactions ..

..Blood will be obtained from the mother for serum dioxin and furans (total plus 17 individual isomers plus WHO TEQs including PCBs, performed by AXYS Analytical Services Ltd...

..is devoted to the investigation and development of novel cycloisomerization approaches toward monocyclic and fused furans, pyrroles, and thiophenes, and to the development of cascade migration/cyclization methodologies en route to ..

..Tetrahydro furans and pyrans are common structural features in a number of important classes of natural product...

..Tetrahydro furans and pyrans are common structural features in a number of important classes of natural product...

..be applied to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles...

..be applied to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles...

..be applied to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles...

..Many of these chemicals that include the dioxins, furans, and polychlorinated biphenyls (PCBs) persist for very long periods of time in the environment and have the ..

..A, vineomycinone B 2, kidamycin and rubiflavin A feature intramolecular [4+2] cycloadditions of sugar-substituted furans with benzynes to give oxabicycloheptadienes that undergo acid-catalyzed rearrangements to furnish C-glycosylated ..

..is devoted to the investigation and development of novel cycloisomerization approaches toward monocyclic and fused furans, pyrroles, and thiophenes, and to the development of cascade migration/cyclization methodologies en route to ..

..is devoted to the investigation and development of novel cycloisomerization approaches toward monocyclic and fused furans, pyrroles, and thiophenes, and to the development of cascade migration/cyclization methodologies en route to ..

..Among the reactions to be studied are [4+2]-cycloaddition reactions of amido and thio-substituted furans and other heteroaromatics as a method for preparing novel azapolycyclic rings...

..basic strategies for the syntheses of these compounds are unique and involve the stereoselective elaboration of furans and hydropyrans derived therefrom, asymmetric cyclopropanations, ring closing metatheses, and vinylogous aldol ..

..for the regio- and stereospecific synthesis of highly substituted heterocycles (dihydro- and tetrahydro- pyrans, furans, piperidines and pyrroles) is proposed...

..by applications to stereocontrolled preparation of polyhydroxylated-piperidines and tetrahydro-pyrans and -furans. In future studies, the preparative potential of oxidative methods for oxonium cation generation will be probed ..

..with the bioactivation of a diverse array of pro-toxins including carcinogenic aromatic amines and pneumotoxic furans, while also maintaining to-hydroxylase selectivity for fatty acids and alkyl hydrocarbons...

..of the dipolar cycloadditions of nitrile oxides will be developed, and extensions of our strategy exploiting furans and hydropyrans as key intermediates for the asymmetric syntheses of natural products and selected skeletal ..

..with the bioactivation of a diverse array of pro-toxins including carcinogenic aromatic amines and pneumotoxic furans, while also maintaining to-hydroxylase selectivity for fatty acids and alkyl hydrocarbons...

..products, which will be accomplished by utilizing [4 + 3] cycloaddition reactions between 2,3-disubstituted furans and vinyl oxocarbenium ions to generate, in a single step, a complex segment of the molecules' unprecedented fused ..

..The project involves novel methods towards the synthesis of 2-amido furans from pyrrolidinone intermediates. Cyclic amides are widely regarded as useful precursors for N-acyliminium ions...

..for the regio- and enantiospecific synthesis of highly substituted heterocycles (dihydro- and tetrahydropyrans, furans, piperidines and pyrroles) is described...

..The proposed methods stem from the unexplored reactivity of electronically rich species, such as dienes and furans, during cycloaddition reactions and highlight the potential of these reactions for the construction of highly ..

..SDE formation and intramolecular heteroatom nucleophile SDE-openings focused on the synthesis of pyrans and furans and will be utilized in the synthesis of psymberin and pectenotoxin 4, which are antitumor agents...