About: Development of Antiviral and Anticancer Drugs with Acyclic Nucleotide Structure: Rational Design Based on Their Interference with Cellular Metabolism.

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About: Development of Antiviral and Anticancer Drugs with Acyclic Nucleotide Structure: Rational Design Based on Their Interference with Cellular Metabolism. Goto Sponge NotDistinct Permalink

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rdf:type	http://linked.opendata.cz/ontology/domain/vavai/Projekt
rdfs:seeAlso	http://www.isvav.cz/projectDetail.do?rowId=GV203/96/K001
Description	The aim of the project is the rational design and synthesis of novel acyclsic nucleotide analogues and their produgs derived from pyrimidine and purine heterocyclic bases with cytostatic, antiviral, antiparasitic, immunomodulatory and/or other biologicalactivities and to study them in experimental models of cancer with different etiology, models of virus and/or protozoan infections in vitro, on resting lymphocytes as well as on immortalised lymphocyte cell lines. In order to rationally proceed with the design and investigation of acyclic nucleotide phosphonates we need to know whether the compounds enter the cell or how to enhance their membrane transport, we must understand what is going on with the compound inside the cell and what are the molecular consequences of its presence. We are convinced that the detailed investigation of nucleoside and nucleotide interconversions in the analog-treated cell lines and systemic qualitative and quantitative investigation of intracellular pool will clarify still (en) Cílem předkládaného projektu je racionální návrh a syntéza nových cyklických nukleotidových analog a jejich profarmak odvozených od pyrimidinových a purinových heterocyklických basí, které mají cytostatickou, protivirovou, antiparasitární, imunomodulačnía jiné biologické aktivity; jejich studium na experimentálních modelech neoplasmie (karcinomy, sarkomy, lymfomy), virových a parasitálních infekcí in vitro a na neproliferujících, proliferujících a imortalizovaných lymfocytech. Praktickým výstupem navrhovaného projektu je nalezení dalších potenciálních chemotherapeutik společensky závažných inemocnění. Projekt je založen na systematické spolupráci mezi chemickou syntézou a biochemickým studiem. Návrhy nových struktur jsou oproštěny od původních empirických přístupů a budou vycházet z poznatků o buněčném transportu, o anabilických přeměnách nových analog v buňce a ze znalosti vlivu těchto struktur na vzájemné metabolické přeměny prekurzorů nukleových kyselin. Jsme přesvědčeni, že zejména systema
Title	Development of Antiviral and Anticancer Drugs with Acyclic Nucleotide Structure: Rational Design Based on Their Interference with Cellular Metabolism. (en) Protivirová a protirakovinová léčiva se strukturou acyklických nukletidových analogů: racionální vývoj založený na jejich zásahu do buněčného metabolismu
skos:notation	GV203/96/K001
http://linked.open...avai/cep/aktivita	Comprehensive projects
http://linked.open...kovaStatniPodpora	http://linked.opendata.cz/resource/domain/vavai/projekt/GV203%2F96%2FK001/celkovaStatniPodpora
http://linked.open...ep/celkoveNaklady	http://linked.opendata.cz/resource/domain/vavai/projekt/GV203%2F96%2FK001/celkoveNaklady
http://linked.open...datumDodatniDoRIV	2002-11-19 (xsd:date)
http://linked.open...i/cep/druhSouteze	VS - Veřejná soutěž ve výzkumu a vývoji
http://linked.open...ep/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open.../cep/fazeProjektu	877063
http://linked.open...ai/cep/hlavniObor	CE - Biochemie
http://linked.open...hodnoceniProjektu	V - Vynikající výsledky (s mezinárodním významem apod.). Zároveň byly splněny cíle a předpokládané výsledky uvedené ve smlouvě / rozhodnutí o poskytnutí podpory.
http://linked.open.../cep/klicovaSlova	Neuvedeno. (en)
http://linked.open...ep/partnetrHlavni	Ústav organické chemie a biochemie AV ČR, v. v. i.
http://linked.open...inujicichPrijemcu	0 (xsd:int)
http://linked.open...cep/pocetPrijemcu	1 (xsd:int)
http://linked.open...ocetSpoluPrijemcu	0 (xsd:int)
http://linked.open.../pocetVysledkuRIV	63 (xsd:int)
http://linked.open...enychVysledkuVRIV	63 (xsd:int)
http://linked.open...iciPoslednihoRoku	2002
http://linked.open...atUdajeProjZameru	2002
http://linked.open...usZobrazovaneFaze	DUU
http://linked.open...ai/cep/typPojektu	P - Projekt výzkumu a vývoje financovaný ze státního rozpočtu
http://linked.open.../cep/vedlejsiObor	CC - Organická chemie FD - Onkologie a hematologie
http://linked.open...jektu+dodavatelem	Řešitelé studovali látky se strukturou acyklických nukleotidových analogů, zejména z hlediska jejich biologické aktivity jako potenciálních léčiv s virostatickým a kancerostatickým účinkem. Některé látky tohoto typu již byly schváleny jako léčiva (Viread (cs)
http://linked.open...tniCyklusProjektu	ZBBBBKU
is http://linked.open...vavai/riv/projekt of	Formation of ternary complexes by coordination of (diethylenetriamine)-Platinum(II) to N1 or N7 of the adenine moiety of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA): Comparison of the acid-base and Metal-ion-binding prop 6-Guanidinopurine nucleosides and their analogues. 6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity. Progress in Acyclic Nucleoside and Nucleotide Chemistry and Application. N/A Magnesium complexes of the antiviral 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and of its 1-, 3-, and 7-deaza analogues in aqueous solution. Modulation of cell progression of antibody production in mouse hybridomas by a nucleotide analogue. Early Carboniferous Rb - Sr mica - whole rock ages of phases of medium- and low-pressure metamorphism in the Saxothuringian zone, western Bohemia. Cross-coupling reactions of 2-amino-6-halopurine derivatives with organometallic reagents leading to 6-alkylated purine acyclic nucleotide analogues. Isoenzymes of GMP kinase from L1210 cells: isolation and characterization. Metal ion-binding properties of the nucleotide analogue 1-[2-(phosphonomethoxy)ethyl]cytosine (PMEC) in aqueous solution. Phosphorylation of enentiomers of HPMPG. Regioselective preparation of N 7 - and N 9 -alkyl derivatives of N 6 -[(dimethylamino)methylene]adenine bearing an active methylene group and their further derivatization leading to .alfa.-branched acyclic nucleoside analogues. Synthesis of quaternary 1-[2(phosphonomethoxy)ethyl] derivates of 2,4-diaminopyrimidine and related acyclic nucleotide analogs. Synthesis of quaternary 1-[2-(phosphonomethoxy)ethyl] derivatives of 2,4-diaminopyrimidine and related acyclic nucleotide analogs. Synthesis of acyclic 9-deazanucleosides: 9-(2,3-dihydroxypropyl)-9-deazahypoxanthine. Synthesis of N 3-substituted isoguanine derivatives of acyclic nucleotide phosphonates. Metal ion-binding properties of 9-(4-phosphonobutyl)adenine (dPMEA), a sister compound of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), and quantification of the equilibria involving four Cu(PMEA) isomers. O -Phosphonatomethylcholine, its analogues, alkyl esters, and their biological activity. Transformation of 8-[(2-hydroxyalkyl)sulfanyl]adenines to 6-amino-7 H -purin-8(9 H )-one derivatives. Antivaccinia activities of acyclic nucleoside phosphonate derivatives in epithelial cells and organotypic cultures. Antiretrovirus activity of a novel class of acyclic pyrimidine nucleoside phosphonates. Synthesis of Acyclic Nucleotide Analogues Derived from 6-Hetarylpurines via Cross-Coupling Reactions of 9-[2-(Diethoxyphosphonylmethoxy)Ethyl]-6-Iodopurine with Hetaryl Organometallic Reagents. Catalytic Hydrogenation Causes C-Benzyl Bond Cleavage in 6-Amino-7,7-dibenzyl-2,4-dimethoxy-7 H -pyrrolo[3,2- d ]pyrimidine: an Example Indicating Novel Route to 6-Amino-7-benzyl-5 H -pyrrolo-[3,2- d ]pyrimidines and Related Compounds. Synthesis and cytostatic activity of substituted 6-phenylpurine bases and nucleosides: application of the Suzuki-Miyaura cross-coupling reactions of 6-chloropurine derivatives with phenylboronic acids. Synthesis of acyclic nucleoside and nucleotide analogs derived from 6-amino-7 H -purin-8(9 H )-one. Synthesis of acyclic adenine 8,N-anhydronucleosides. Synthesis of acyclic nucleotide analogues derived from 2-amino-6- C -substituted purines via cross-coupling reactions of 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-halopurines with diverse organometallic reagents. Synthesis and biological activity of 2- and 6- C -substituted purine bases, nucleosides and acyclic nucleotide analogues. Synthesis of acyclic nucleoside and nucleotide analogs derived from 6-amino-7 H -purine-8(9 H )-thione and 8-(methylsulfanyl)adenine. Synthesis of acyclic nucleotide analogues derived from N 3 -substituted isoguanine. Ternary copper(II) complexes in solution [1,2] formed with 8-aza derivatives of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). Antitumor activity of N6-substituted PMEDAP derivatives against T-cell lymphoma Antitumour activity of a combined treatment with PMEDAP and docetaxel in the Prague inbred Sprague-Dawley/cub rat strain bearing T-cell lymphoma A facile synthesis of azetidin-2-ylphosphonic acid and its 1-alkyl derivatives. An alternative synthesis of HPMPC and HPMPA diphosphoryl derivatives. Activation by 9-( R )-[2-(phosphonomethoxy)propyl]adenine of chemokine (RANTES, macrophage inflammatory protein 1.alfa.) and cytokine (tumor necrosis factor alpha, interleukin-10 [IL-10], IL-1.beta.) production. Antitumor Activity of a Combined Treatment with PMEDAP and Docetaxel in the Prague Inbred Sprague-Dawley/Cub Rat Strain Bearing T-cell Lymphoma. Synthesis of 8-amino- and N -substituted 8-aminoadenine derivatives of acyclic nucleoside and nucleotide analogs. Synthesis and cytostatic activity of N -[2-(phosphonomethoxy)alkyl]derivatives of N 6 -substituted adenines, 2,6-diaminopurines and related compounds. Synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleoside and nucleotide analogs. Alkylation of 8-substituted purine bases. Nonproteolyzed form of DNA-polymerase .SIGMA. from T-cell spontaneous lymphoma of Sprague-Dawley inbred rat: isolation and characterization. Simple Method for Cleavage of Phosphonic Acid Diesters to Monoesters. Synthesis of acyclic nucleotide analogues derived from 6-( sec - or tert -alkyl)purines via coupling of 6-chloropurine derivatives with organocuprates. An alternative synthesis of HPMPC and HPMPA diphosphoryl derivatives. Aspects of the co-ordination chemistry of the antiviral nucleotide analogue, 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP). Acyclic nucleotide analogues suppress growth and induce apoptosis in human leukemia cell lines. HPMPApp as a substrate toward replicative DNA polymerases .alfa., .delta. and .epsilon. Inhibitory potency of 5-benzyluracil, 5-phenylcytosine and 5-phenylpyrimidin-2-one nucleosides against uridine phosphorylase from mouse leukemic L1210 cells. Perfluoroalkylation of 6-iodopurines by trimethyl(perfluoroalkyl)purine bases, nucleosides and acyclic nucleotide analogues. Structure-antiviral activity relationship in the series of pyrimidine and purine N -[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1.Derivatives substituted at the carbon atoms of the base. 7-(1-cyanobut-3-en-1-yl)- N 6 -[ N,N -dimethylamino)methylene]-adenine as a starting compound for the synthesis of .alfa.-branched acyclic analogues of N 7 -isomer of adenosine. 9-[2-(Phosphonomethoxy)ethyl]adenine diphosphate (PMEApp) as a substrate toward replicative DNA polymerases .alfa., .beta., .elem., and .elem.*. Anticancer Effect of PMEDAP - Monitoring of Apoptosis. 9-[2-(Phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP) - a Potential Drug against Hematological Malignancies - Induces Apoptosis. Cytostatic 6-arylpurine nucleosides II. Synthesis of sugar-modified derivatives: 9-(2-deoxy-.beta.-D- erythro -pentofuranosyl)-, 9-(5-deoxy-.beta.-D-ribofuranosyl)- and 9-(2,3-dihydroxypropyl)-6-phenylpurines. Interaction of Guanine Phosphonomethoxyalkyl Derivatives with GMP Kinase Isoenzymes. Macrophage activation by antiviral acyclic nucleoside phosphonates in dependence on priming immune stimuli. Phosphorylation of purine (phosphonomethoxy)alkyl derivatives by mitochondrial AMP kinase (AK2 type) from L1210 cells. Cytostatic 6-arylpurine nucleosides III. Synthesis and structure-activity relationship study in cytostatic activity of 6-aryl-, 6-hetaryl- and 6-benzylpurine ribonucleosides. Intramolecular stacking interactions in ternary copper(II) complexes formed with 2,2'-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA), the carba relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine Interactions of 1-[( S )-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir) diphosphate with DNA polymerases .alfa., .delta. and .elem.. Metal ion-binding properties of 1-methyl-4-aminobenzimidazole (=9-methyl-1,3-dideazaadenine) and 1,4-dimethylbenzimidazole (=6,9-dimethyl-1,3-dideazapurine). Quantification of the steric effect of the 6-amino group on metal ion binding at the N7 site of
is http://linked.open...vavai/cep/projekt of	http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/1996/ico%3A61388963 http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/1997/ico%3A61388963 http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/1998/ico%3A61388963 http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/1999/ico%3A61388963 http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/2000/ico%3A61388963 http://linked.opendata.cz/resource/domain/vavai/cep/ucast/GV203%2F96%2FK001/2001/ico%3A61388963

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