6-Azathymine

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform

M B Pedersen - One of the best experts on this subject based on the ideXlab platform.

  • The dominant mutation Suppressor of black indicates that de novo pyrimidine biosynthesis is involved in the Drosophila tan pigmentation pathway.
    Molecular Genetics and Genomics, 1993
    Co-Authors: Jožica Piškur, D Kolbak, Lars Sondergaard, M B Pedersen
    Abstract:

    A deficiency in the production of β-alanine causes the black (b) phenotype of Drosophila melanogaster. This phenotype is normalized by a semi-dominant mutant gene Su(b) shown previously to be located adjacent to or within the rudimentary (r) locus. The r gene codes for three enzyme activities involved in de novo pyrimidine biosynthesis. Pyrimidines are known to give rise to β-alanine. However, until recently it has been unclear whether de novo pyrimidine biosynthesis is directly coupled to β-alanine synthesis during the tanning process. In this report we show that flies carrying Su(b) can exhibit an additional phenotype, resistance to toxic pyrimidine analogs (5-fluorouracil, 6-Azathymine and 6-azauracil). Our interpretation of this observation is that the pyrimidine pool is elevated in the mutant flies. However, enzyme assays indicate that r enzyme activities are not increased in Su(b) flies. Genetic mapping of the Su(b) gene now places the mutation within the r gene, possibly in the carbamyl phosphate synthetase (CPSase) domain. The kinetics of CPSase activity in crude extracts has been studied in the presence of uridine triphosphate (UTP). While CPSase from wild-type flies was strongly inhibited by the end-product, UTP, CPSase from Su(b) was inhibited to a lesser extent. We propose that diminished end-product inhibition of de novo pyrimidine biosynthesis in Su(b) flies increases available pyrimidine and consequently the β-alanine pool. Normalization of the black phenotype results.

  • The dominant mutation Suppressor of black indicates that de novo pyrimidine biosynthesis is involved in the Drosophila tan pigmentation pathway.
    Molecular & general genetics : MGG, 1993
    Co-Authors: Jožica Piškur, D Kolbak, Lars Sondergaard, M B Pedersen
    Abstract:

    A deficiency in the production of beta-alanine causes the black (b) phenotype of Drosophila melanogaster. This phenotype is normalized by a semi-dominant mutant gene Su(b) shown previously to be located adjacent to or within the rudimentary (r) locus. The r gene codes for three enzyme activities involved in de novo pyrimidine biosynthesis. Pyrimidines are known to give rise to beta-alanine. However, until recently it has been unclear whether de novo pyrimidine biosynthesis is directly coupled to beta-alanine synthesis during the tanning process. In this report we show that flies carrying Su(b) can exhibit an additional phenotype, resistance to toxic pyrimidine analogs (5-fluorouracil, 6-Azathymine and 6-azauracil). Our interpretation of this observation is that the pyrimidine pool is elevated in the mutant flies. However, enzyme assays indicate that r enzyme activities are not increased in Su(b) flies. Genetic mapping of the Su(b) gene now places the mutation within the r gene, possibly in the carbamyl phosphate synthetase (CPSase) domain. The kinetics of CPSase activity in crude extracts has been studied in the presence of uridine triphosphate (UTP). While CPSase from wild-type flies was strongly inhibited by the end-product, UTP, CPSase from Su(b) was inhibited to a lesser extent. We propose that diminished end-product inhibition of de novo pyrimidine biosynthesis in Su(b) flies increases available pyrimidine and consequently the beta-alanine pool. Normalization of the black phenotype results.

U. Stottmeister - One of the best experts on this subject based on the ideXlab platform.

  • Photolysis of metribuzin in oxygenated aqueous solutions
    Chemosphere, 1998
    Co-Authors: U. Raschke, G. Werner, H. Wilde, U. Stottmeister
    Abstract:

    Abstract The photochemical behaviour of metribuzin [4-amino-6-(1.1-dimethylethyl)-3-methylthio-1.2.4-triazin-5(4H)-one] and its known metabolites desaminometribuzin (DA), diketometribuzin (DK) and desaminodiketometribuzin (DADK) was investigated in aqueous oxygenated solutions at various pH values. The photochemical degradation of metribuzin over time and the formation and further fate of DA, DK and DADK were elucited. Both side-chain degradation and ring opening were detected as a result of photolysis. Six unknown metabolites as a result of side-chain degradation, including 6-azauracile, 6-Azathymine and 4-aminosubstituted derivatives, were identified as very stable photodegradation products. Furthermore, some inorganic and organic ionic compounds were detected such as monocarboxylic, dicarboxylic and ketocarboxylic acids formed by side-chain degradation and ring cleavage.

  • Photodecomposition of 4-amino-1,2,4-triazin-3,5-diones and -thiones in oxygenated aqueous solutions
    Journal of Photochemistry and Photobiology A: Chemistry, 1998
    Co-Authors: U. Raschke, G. Werner, H. Wilde, U. Stottmeister
    Abstract:

    Abstract The photodecomposition of newly synthesized 4-amino-1,2,4-triazinthione 1 and -dione 2 was examined in oxygenated aqueous solutions at various pH values. The degradation pathway of these compounds was compared with the photochemical decomposition of the herbicide metribuzin. Side-chain degradation by deamination, decarboxylation, sulfoxidation and dealkylation is typical for photolysis. Structurally similar compounds display substantial differences with respect to degradation. The pH value has an accelerating or inhibiting effect on the degradation rate. After the rapid formation of basic metabolites by the deamination of 1 and the decarboxylation of 2, selective decomposition takes place in alkaline and acidic solutions, whereas a non-selective course was detected under neutral conditions. The radicalic mechanisms of important reaction steps are discussed. Several metabolites with intact heterocyclic ring systems were identified as photochemically stable final products by the addition of a standard compound, such as 6-azauracile or 6-Azathymine. In contrast to side-chain degradation, ring cleavage was only observed after long irradiation times. Carboxylic and ketocarboxylic acids as well as some inorganic ions were identified in the irradiated solution as the degradation products of side-chain degradation and ring cleavage.

Jožica Piškur - One of the best experts on this subject based on the ideXlab platform.

  • The dominant mutation Suppressor of black indicates that de novo pyrimidine biosynthesis is involved in the Drosophila tan pigmentation pathway.
    Molecular Genetics and Genomics, 1993
    Co-Authors: Jožica Piškur, D Kolbak, Lars Sondergaard, M B Pedersen
    Abstract:

    A deficiency in the production of β-alanine causes the black (b) phenotype of Drosophila melanogaster. This phenotype is normalized by a semi-dominant mutant gene Su(b) shown previously to be located adjacent to or within the rudimentary (r) locus. The r gene codes for three enzyme activities involved in de novo pyrimidine biosynthesis. Pyrimidines are known to give rise to β-alanine. However, until recently it has been unclear whether de novo pyrimidine biosynthesis is directly coupled to β-alanine synthesis during the tanning process. In this report we show that flies carrying Su(b) can exhibit an additional phenotype, resistance to toxic pyrimidine analogs (5-fluorouracil, 6-Azathymine and 6-azauracil). Our interpretation of this observation is that the pyrimidine pool is elevated in the mutant flies. However, enzyme assays indicate that r enzyme activities are not increased in Su(b) flies. Genetic mapping of the Su(b) gene now places the mutation within the r gene, possibly in the carbamyl phosphate synthetase (CPSase) domain. The kinetics of CPSase activity in crude extracts has been studied in the presence of uridine triphosphate (UTP). While CPSase from wild-type flies was strongly inhibited by the end-product, UTP, CPSase from Su(b) was inhibited to a lesser extent. We propose that diminished end-product inhibition of de novo pyrimidine biosynthesis in Su(b) flies increases available pyrimidine and consequently the β-alanine pool. Normalization of the black phenotype results.

  • The dominant mutation Suppressor of black indicates that de novo pyrimidine biosynthesis is involved in the Drosophila tan pigmentation pathway.
    Molecular & general genetics : MGG, 1993
    Co-Authors: Jožica Piškur, D Kolbak, Lars Sondergaard, M B Pedersen
    Abstract:

    A deficiency in the production of beta-alanine causes the black (b) phenotype of Drosophila melanogaster. This phenotype is normalized by a semi-dominant mutant gene Su(b) shown previously to be located adjacent to or within the rudimentary (r) locus. The r gene codes for three enzyme activities involved in de novo pyrimidine biosynthesis. Pyrimidines are known to give rise to beta-alanine. However, until recently it has been unclear whether de novo pyrimidine biosynthesis is directly coupled to beta-alanine synthesis during the tanning process. In this report we show that flies carrying Su(b) can exhibit an additional phenotype, resistance to toxic pyrimidine analogs (5-fluorouracil, 6-Azathymine and 6-azauracil). Our interpretation of this observation is that the pyrimidine pool is elevated in the mutant flies. However, enzyme assays indicate that r enzyme activities are not increased in Su(b) flies. Genetic mapping of the Su(b) gene now places the mutation within the r gene, possibly in the carbamyl phosphate synthetase (CPSase) domain. The kinetics of CPSase activity in crude extracts has been studied in the presence of uridine triphosphate (UTP). While CPSase from wild-type flies was strongly inhibited by the end-product, UTP, CPSase from Su(b) was inhibited to a lesser extent. We propose that diminished end-product inhibition of de novo pyrimidine biosynthesis in Su(b) flies increases available pyrimidine and consequently the beta-alanine pool. Normalization of the black phenotype results.

Alan C. Sartorelli - One of the best experts on this subject based on the ideXlab platform.

Hoong-chien Lee - One of the best experts on this subject based on the ideXlab platform.

  • Functional Module Connectivity Map (FMCM): a framework for searching repurposed drug compounds for systems treatment of cancer and an application to colorectal adenocarcinoma.
    PloS one, 2014
    Co-Authors: Feng-hsiang Chung, Yun-ru Chiang, Ai-lun Tseng, Yung-chuan Sung, Min-chang Huang, Hoong-chien Lee
    Abstract:

    Drug repurposing has become an increasingly attractive approach to drug development owing to the ever-growing cost of new drug discovery and frequent withdrawal of successful drugs caused by side effect issues. Here, we devised Functional Module Connectivity Map (FMCM) for the discovery of repurposed drug compounds for systems treatment of complex diseases, and applied it to colorectal adenocarcinoma. FMCM used multiple functional gene modules to query the Connectivity Map (CMap). The functional modules were built around hub genes identified, through a gene selection by trend-of-disease-progression (GSToP) procedure, from condition-specific gene-gene interaction networks constructed from sets of cohort gene expression microarrays. The candidate drug compounds were restricted to drugs exhibiting predicted minimal intracellular harmful side effects. We tested FMCM against the common practice of selecting drugs using a genomic signature represented by a single set of individual genes to query CMap (IGCM), and found FMCM to have higher robustness, accuracy, specificity, and reproducibility in identifying known anti-cancer agents. Among the 46 drug candidates selected by FMCM for colorectal adenocarcinoma treatment, 65% had literature support for association with anti-cancer activities, and 60% of the drugs predicted to have harmful effects on cancer had been reported to be associated with carcinogens/immune suppressors. Compounds were formed from the selected drug candidates where in each compound the component drugs collectively were beneficial to all the functional modules while no single component drug was harmful to any of the modules. In cell viability tests, we identified four candidate drugs: GW-8510, etacrynic acid, ginkgolide A, and 6-Azathymine, as having high inhibitory activities against cancer cells. Through microarray experiments we confirmed the novel functional links predicted for three candidate drugs: phenoxybenzamine (broad effects), GW-8510 (cell cycle), and imipenem (immune system). We believe FMCM can be usefully applied to repurposed drug discovery for systems treatment of other types of cancer and other complex diseases.

  • Viability test of colon and breast cancer cells treated with single drug.
    2014
    Co-Authors: Feng-hsiang Chung, Yun-ru Chiang, Ai-lun Tseng, Yung-chuan Sung, Min-chang Huang, Hoong-chien Lee
    Abstract:

    Tests were conducted on eight drugs: phenoxybenzamine (PB), GW-8510, phthalylsulfathiazole (PS), etacrynic acid (EA), ginkgolide A (GA), triflusal (TF), imipenem (IM), and 6-Azathymine (6-AT), with concentrations of 0, 0.1, 1, 10, and 30 µM. (A) Viability of MCF7 on treatment of the eight drugs. (B) Viability of five cell lines on treatment of GW-8510. Colon cancer cells HCT116, RKO, SW403 and SW620, and the breast cancer cell MCF7, were treated with single drug for 5 days. After 5 days, proliferation activities of these cells were detected by Alamar Blue assay.

  • Predicted drug compounds for colorectal cancer adenoma.
    2014
    Co-Authors: Feng-hsiang Chung, Yun-ru Chiang, Ai-lun Tseng, Yung-chuan Sung, Min-chang Huang, Hoong-chien Lee
    Abstract:

    The eight GO terms (biological function classifications) included are APO, CC, CP, ST, TR, DR, CP, RM and ISP (see abbreviations below). All drugs in the table have ES (enrichment score) 0) on any of the GO functions. Only compounds with up to 6 components are given. Abbreviations: ISP: immune system process – trifusal or morantel or gingolide or cetirizine or imipenem; APO: apoptosis – irinotecan or doxazosin or cycloserine or repaglinide; CC: cell cycle – doxorubicin or withaferin A; ST: signal transduction – 6-Azathymine or tyloxapol; TR: transcription – sanguinarine; DR: DNA replication – piperlongumine; CP: Cell proliferation – bepridil; RM: RNA metabolic process – skimmianine; TDNA: transcription and DNA replication –chrysin or thioguanosine or luteolin or thiostrepton or sulconazole. The “degrees” in “Ratio of degrees” indicate the number of functional modules to which the corresponding component is beneficial.