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1.
Bioorg Khim ; 29(2): 181-9, 2003.
Artículo en Ruso | MEDLINE | ID: mdl-12708318

RESUMEN

1-(2,3,5-Tri-O-acetyl)-beta-D-ribofuranosyl indole, the key compound in the synthesis of glycosides with the bis(indole) aglycone, was obtained for the first time by the indoline-indole method. There were synthesized 3-(1-methylindol-3-yl)-4-(1-glycosylindol-3-yl)furan(or pyrrole)-2,5-diones containing the residue of beta-D-ribofuranose or 2-deoxy-beta-D-ribofuranose and analogous glycosides of indolo[2,3-a]furano(or pyrrolo)[3,4-c]carbazol-5,7-diones, which are structurally relative to the antitumor antibiotic rebeccamycin. Their cytotoxicities toward a number of human tumor cell lines were studied in vitro, and the carbazole N-glycosides were shown to be more active than the bis-(indole) glycosides. At the same time, the ribofuranosides were found to be less active than the corresponding ribopyranosides synthesized previously.


Asunto(s)
Aminoglicósidos , Antineoplásicos/química , Antineoplásicos/farmacología , Indoles , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Bioquímica/métodos , Carbazoles/química , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Furanos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Pirroles/química , Pirroles/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas
2.
Bioorg Khim ; 22(10-11): 832-7, 1996.
Artículo en Ruso | MEDLINE | ID: mdl-9036842

RESUMEN

A synthesis of 3-(1H-3-indolyl)-4-(1-glycosyl-3-indolyl)furan-2,5-diones and -1H-pyrrole-2,5-diones modified with the residues of D-ribo-, D-xylo-, L-arabino-, D-galactopyranose, and D-lactose was described. Influence of the compounds prepared on DNA biosynthesis in CaOv cells was studied.


Asunto(s)
Antineoplásicos/síntesis química , Glicósidos/síntesis química , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Glicósidos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Células Tumorales Cultivadas/efectos de los fármacos
3.
Bioorg Khim ; 22(6): 458-67, 1996 Jun.
Artículo en Ruso | MEDLINE | ID: mdl-8975674

RESUMEN

A synthesis of the derivatives of bis(indolyl)furan and bis(indolyl)pyrrole, which contain an acyclic fragment or a residue of D-ribo-, D-xylo-, L-arabino-, D-galactopyranose, or D-lactose was described. Bis(indole) aglycone was created using 1-glycosylindoles, which were synthesized by the indoline-indole method.


Asunto(s)
Glicósidos/síntesis química , Glicósidos/farmacología , Indoles/síntesis química , Indoles/farmacología , División Celular/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas
4.
Bioorg Khim ; 21(8): 617-24, 1995 Aug.
Artículo en Ruso | MEDLINE | ID: mdl-8540902

RESUMEN

Interaction of 3'-amino-3'-deoxy-2',3'-secoadenosine with the N-hydroxysuccinimide esters of nicotinic or quinaldic acids and with 1-nitroanthraquinone-2-carboxylic acid in the presence of 2-ethoxy-1-ethoxy-carbonyl-1,2-dihydroquinoline led to the corresponding amides. To obtain 5'-modified 2',3'-secoadenosine analogs, 5'-deoxy-5'-nicotinoylamido-, 5'-deoxy-5'-(quinoline-2- carbonylamido)-, and 5'-deoxy-5'-[3-(3-indolyl)propionylamido]adenosine were subjected to the periodate oxidation--sodium borohydride reduction procedure. Structures of the synthesized compounds were was confirmed by 1H NMR spectroscopy, 2',3'-Diamino-2',3'-deoxy-, 3'-deoxy-3'-(quinoline-2-carbonylamido)-, and 5'-deoxy-5'-[3-(3-indolyl)propionylamido]-2',3'-secoadenosines+ ++ exhibited a cytotoxic effect on CaOv cells in vitro (CE50 10-30 microM).


Asunto(s)
Adenosina/análogos & derivados , Antineoplásicos/síntesis química , Acilación , Adenosina/síntesis química , Adenosina/farmacología , Antineoplásicos/farmacología , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Neoplasias Ováricas/patología , Células Tumorales Cultivadas
5.
Bioorg Khim ; 21(8): 625-31, 1995 Aug.
Artículo en Ruso | MEDLINE | ID: mdl-8540903

RESUMEN

O-Quinaldoyl derivatives of thymidine, 2'-deoxyuridine, and 5-trimethylsilyl-2'-deoxyuridine were synthesized. 5'-Deoxy-5'-(quinoline-2-carbonylamino)- and 5'-deoxy-5'-[(quinoline-2-carbonylamino)butyroylamino]thymidine were obtained by the reaction of 5'-amino-5'-deoxythymidine with pentafluorophenyl ester of quinaldic acid, or with 4-(quinoline-2-carbonylamino)butyric acid. Antiproliferative properties in respect to CaOv cells in vitro were found in most of the synthesized quinaldoyl derivatives of nucleosides (CE50 approximately 10(-5) M). 3'-O-Quinaldoylthymidine exhibited an antitumor activity in vivo. The interaction of 3'- and 5'-O-quinaldoyl- as well as 3',5'-di-O-quinaldoylthymidine with DNA was investigated by the method of fluorescent probes.


Asunto(s)
Antineoplásicos/síntesis química , Desoxiuridina/análogos & derivados , Desoxiuridina/síntesis química , Quinolinas/química , Timidina/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Pollos , ADN/química , ADN/efectos de los fármacos , Desoxiuridina/química , Desoxiuridina/farmacología , Femenino , Humanos , Conformación de Ácido Nucleico , Neoplasias Ováricas/patología , Timidina/química , Timidina/farmacología , Células Tumorales Cultivadas
6.
Bioorg Khim ; 21(6): 461-7, 1995 Jun.
Artículo en Ruso | MEDLINE | ID: mdl-7661871

RESUMEN

The reaction of 5'-amino-2',5'-dideoxyuridine and 5'-amino-5'-deoxy-2',3'-O-ethoxymethyliden-6- azauridine with 3-(3-indolyl)propionic or 1-nitroanthraquinon-2-carboxylic acids in THF in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) resulted in the corresponding amide derivatives. The reaction conditions of the standard procedure for the removal of the O-alkylidene protecting group turned out to be too severe for the 5'-N-acylamide derivatives of 6-azauridine. 5'-Deoxy-5'-[3-(3-indolyl)propionyl-amino]-6-azauridine was synthesized from 5'-amino-5'-deoxy-6-azauridine and 3-(3-indolyl)propionic acid in THF in the presence of EEDQ. A reaction between 5'-O-tosyl-2',3'-O-ethoxymethyliden-6-azauridine and 3-aminopropanol gave 3-(3-hydroxypropylamino)-2-(2',3'-O-ethoxymethylidene-beta- D-ribofuranosyl)-as-triazine-5(2H)-one, the structure of which was confirmed also by synthesis from O2,5'-anhydronucleoside and 3-aminopropanol followed by further chemical transformations. A reaction of 3-(3-hydroxypropylamino) derivative obtained with nicotinoyl chloride prepared in situ, or with 1-nirtoanthraquinon-2-carboxylic acid in the presence of DCC with subsequent deprotection, afforded 3-[(3-pyridin-3-ylcarboxy)propylamino]- or 3-[3-(1-nitroanthraquinon-2-carboxy)propylamino]-2-beta-D-ribof ura nosyl-as- triazine-5(2H)-one, respectively. Structures of the nucleosides prepared were examined by 1H NMR spectroscopy. 2',5'-Dideoxy-5'-[(1-nitroanthraquinon-2-carbonyl)amino]uridine at a 10(-4) M concentration was shown to inhibit thymidine incorporation into cell DNA (CE50 10(-5) M) by 72%.


Asunto(s)
Antraquinonas/química , Ácidos Carboxílicos/química , Desoxiuridina/química , Indoles/química , Ácidos Nicotínicos/química , Propionatos/química , Nucleósidos de Pirimidina/química , Aminas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Desoxiuridina/farmacología , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Nucleósidos de Pirimidina/farmacología , Células Tumorales Cultivadas
7.
Bioorg Khim ; 21(4): 289-95, 1995 Apr.
Artículo en Ruso | MEDLINE | ID: mdl-7786320

RESUMEN

Interaction of nicotinoyl chloride in situ with 2'-deoxyuridine, its 3'-O-acetyl-, or 5'-O-trityl derivatives led to 3'-O-nicotinoyl-, 5'-O-nicotinoyl-, 3',5'-di-O-nicotinoyl-, and N3,3'-di-O-nicotinoyl-2'-deoxyuridine. Similarly, 5'-O-nicotinoyl-6-azauridine resulted from the reaction of 2',3'-O-ethoxymethylidene-6-azauridine followed by the deprotection. Reaction of 5'-amino-5'-deoxy-2',3'-O-ethoxymethylidene-6-azauridine with nicotinic acid in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline followed by the cleavage of the 2',3'-O-protecting group gave 5'-deoxy-5'-nicotinamido-6-azauridine. The same compound was obtained from 5'-amino-5'-deoxy-6-azauridine and N-succinimidyl nicotinate. Structures of the compounds obtained were corroborated by 1H NMR spectra. It is shown that 3',5'-di-O-nicotinoyl-2'- deoxyuridine and 5'-deoxy-5'-O-nicotinamido-6-azauridine are cytotoxic toward CaOv cells in vitro (CE50 10(-5) M).


Asunto(s)
Antineoplásicos/química , Niacina/análogos & derivados , Nucleósidos de Pirimidina/química , Antineoplásicos/farmacología , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Niacina/química , Neoplasias Ováricas/patología , Nucleósidos de Pirimidina/farmacología , Células Tumorales Cultivadas
8.
Bioorg Khim ; 21(1): 45-8, 1995 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-7710424

RESUMEN

The interaction of 3'-amino-2',3'-dideoxy- or 5'-amino-2',5'-dideoxy-5-substituted pyrimidine nucleosides with N-ethylmaleimide in DMF in the presence of Et3N gave two diastereomeric 2',3'-dideoxy-3'-(N-ethylsuccinimido)- or 2',5'-dideoxy-5'-(N-ethylsuccinimido)aminonucleosides in each reaction. For 3'-amino-5-trimethylsilyl- and 3'-amino-5-benzyloxymethyl-2',5'-dideoxyuridine diastereomeric 3'-(N-ethylsuccinimido)derivatives were separated by preparative TLC. Structures of synthesized analogs were confirmed by UV-, IR- and 1H-NMR spectra. It has been shown that modified nucleosides at 10(-5)-10(-4) M concentrations do not inhibit the thymidine incorporation into DNA of CaOv cells in vitro.


Asunto(s)
Antimetabolitos Antineoplásicos/síntesis química , Carbohidratos/química , Didesoxinucleósidos/química , Nucleósidos de Pirimidina/química , Antimetabolitos Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Cromatografía en Capa Delgada , Femenino , Humanos , Neoplasias Ováricas/patología , Análisis Espectral , Estereoisomerismo , Células Tumorales Cultivadas
9.
Bioorg Khim ; 18(3): 444-8, 1992 Mar.
Artículo en Ruso | MEDLINE | ID: mdl-1524593

RESUMEN

Glycosylation of trimethylsilyl derivatives of 5-benzyloxymethyl- and 5-hydroxymethyluracil with 3-azido-2,3-dideoxy-5-O-benzoyl-D-ribofuranosyl chloride (prepared from ethyl 3-azido-2,3-dideoxy-5-O-benzoyl-D-ribofuranoside) and subsequent deacylation gave in both cases a mixture of anomeric 3'-azido-2',3'-dideoxy-5-benzyloxymethyl-or 5-hydroxymethyluridines. The anomers were separated by preparative TLC and their structures were studied by UV, IR and 1H-NMR spectroscopy. It is shown that 1-(3-azido-2,3-dideoxy-alpha-D-ribofuranosyl)-5-benzyloxymethyluracil has cytotoxic activity in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA of CaOv cells on 78.6-95.2%.


Asunto(s)
Antivirales/síntesis química , Supervivencia Celular/efectos de los fármacos , Zidovudina/análogos & derivados , Antivirales/farmacología , Línea Celular , Cromatografía en Capa Delgada , ADN/metabolismo , Glicosilación , Espectroscopía de Resonancia Magnética , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Timidina/metabolismo , Zidovudina/síntesis química , Zidovudina/farmacología
10.
Bioorg Khim ; 17(11): 1526-33, 1991 Nov.
Artículo en Ruso | MEDLINE | ID: mdl-1667356

RESUMEN

The reaction of 2'-deoxy-5-trimethylsilyl(Tms)uridine with methanesulfonyl chloride led to the corresponding 3',5'-di-O-mesyl derivative, which was treated with lithium toluylate in DMF to give 2,3'-anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofurano- syl)-5-Tms-uracil. Under these conditions 1-(2,3-dideoxy-5-O-p-toluyl-alpha-D- glycero-pent-2-enofuranosyl)-5-Tms-uracil was obtained from 1-(2-deoxy-alpha-D-ribofuranosyl)-5-Tms-uracil. Interaction of 2,3'-anhydronucleoside with LiN3 in DMF and successive deacylation with MeONa-MeOH gave 3'-azido-2',3'-dideoxy-5-Tms-uridine. Hydrogenation of this compound with 10% Pd/C in ethanol gave 3'-azido-2',3'-dideoxy-5-Tms-uridine. From 2,4,5-tris-Tms-uracil and 2,3-didehydrofurane in 1,2-dichloroethane in the presence of SnCl4 1-(2-tetrahydrofuranyl)-5-Tms-uracil was prepared. In a similar way 1-[(1,3-dioxy-2-propoxy)methyl]-5-Tms-uracil was synthesized by condensation of silylated uracil with 1,3-dibenzyloxy-2-acetoxymethylglycerol followed by the hydrogen transfer hydrogenolysis with cyclohexene--20% Pd(OH)2/C. None of the compounds exhibits cytotoxic activity against CaOv in vitro. The acycloderivative in concentration of 250 micrograms/ml has no effect on the HSV-1 and vaccinia virus replication in vitro. 3'-Azidonucleoside in dose of 100-750 mg/kg as well as 1-(2-tetrahydrofuranyl)-5-Tms-uracil in dose of 160-800 mg/kg were devoid of antitumour activity against P388 in vivo.


Asunto(s)
Antimetabolitos , Glicósidos/química , Nucleósidos/química , Compuestos de Trimetilsililo/química , Uracilo/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antivirales/química , Antivirales/farmacología , Indicadores y Reactivos , Leucemia P388 , Nucleósidos/farmacología , Simplexvirus/efectos de los fármacos , Simplexvirus/fisiología , Compuestos de Trimetilsililo/farmacología , Uracilo/farmacología , Virus Vaccinia/efectos de los fármacos , Virus Vaccinia/fisiología , Replicación Viral/efectos de los fármacos
11.
Bioorg Khim ; 17(8): 1101-10, 1991 Aug.
Artículo en Ruso | MEDLINE | ID: mdl-1750837

RESUMEN

5-Benzyloxymethyl(Bom)-2'-deoxyuridine and its alpha-anomer were used as the key compounds for syntheses of thymidine analogues or 3'-derivatives. Anomeric 5-Bom-2'-deoxyuridines were synthesized from 5-Bom-uracil and 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribo-furanosyl chloride by means of the silyl method. 5-Bom-2'-deoxyuridine was transformed successively to 3',5'-di-O-mesyl derivative, 2,3'-anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofuranosyl)-5-Bom-uracil and 3'-azido-2',3'-dideoxy-5-Bom-uridine. Treatment of the last with SnCl4 in methylene dichloride--methanol led to 3'-azido-2',3'-dideoxy-5-methoxymethyluridine. Under the same conditions the 5-methoxymethyl derivative was obtained from 3',5'-di-O-p-toluyl-5-Bom-2'-deoxyuridine. Interaction of 1-(2-deoxy-alpha-D-ribofuranosyl)-4-Bom-uracil with SnCl4 in methylene dichloride as well as the hydrogen transfer hydrogenolysis in the presence of cyclohexene and Pd(OH)2/C in ethanol led to 1-(2-deoxy-alpha-D-ribofuranosyl)-5-hydroxymethyluracil. Only 3'-azido-2',3'-dideoxy-5-Bom-uridine showed a cytotoxic activity against CaOv cells in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA by 78.8-95.1%. Elucidation of antitumor activity in vivo showed that this nucleoside inhibits growth of solid tumours, Ca755 and LLC, by 79 and 79-83%, respectively, but has no therapeutic effect against lympholeukemia P388.


Asunto(s)
Carbohidratos/química , Desoxiuridina/química , Desoxiuridina/síntesis química , Espectroscopía de Resonancia Magnética
12.
Antibiot Khimioter ; 36(3): 28-9, 1991 Mar.
Artículo en Ruso | MEDLINE | ID: mdl-1877872

RESUMEN

The data on UV, 1H NMR and mass spectroscopy confirmed that heliomycin produced by S. heliomycini and antibiotic 11-98 produced by S. olivocinereus were identical with resistomycin. The major minor component produced by S. heliomycini was shown to be resistoflavin which was also confirmed by physicochemical methods.


Asunto(s)
Antibacterianos/química , Compuestos Policíclicos/química , Streptomyces/metabolismo , Antibacterianos/biosíntesis , Benzopirenos/química , Cromatografía
13.
Bioorg Khim ; 15(11): 1569-72, 1989 Nov.
Artículo en Ruso | MEDLINE | ID: mdl-2624594

RESUMEN

Condensation of daunorubicin or its (13 R, S)-dihydro derivative with inosine dialdehyde in the presence of NaBH3CN yielded novel derivatives of anthracycline antibiotics with incorporated inosine residue: 3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)-hydroxymethylmorpholino-N4"]- daunorubicin and (13 R,S)-dihydro-3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)- hydroxymethylmorpholino-N4"]-daunorubicin. The compounds did not inhibit growth of Bacillus mycoides and were less cytotoxic in vitro and less toxic in vivo than the parent antibiotics.


Asunto(s)
Daunorrubicina/análogos & derivados , Inosina , Antibióticos Antineoplásicos/farmacología , Bacillus/efectos de los fármacos , Fenómenos Químicos , Química , Daunorrubicina/farmacología , Espectroscopía de Resonancia Magnética
14.
Bioorg Khim ; 15(10): 1423-30, 1989 Oct.
Artículo en Ruso | MEDLINE | ID: mdl-2631686

RESUMEN

Streptomyces grisoruber strain 1618-306 produces three types of anthracycline antibiotics, derivatives of epsilon-pyrromycinone (methyl (7S, 9R, 10R)-9-ethyl-5,7,8,9,10,12-hexahydro-1,4,6,7,9-pentahydroxy-5,12-di oxo-10- naphthacenecarboxylate), epsilon-1-hydroxyauramycinone and epsilon-1-hydroxysulfurmycinone, differing in C-9 substituent in D ring of anthracyclines (Et, Met or CH2COCH3, respectively). Besides 7-O-glycosides of these aglycones, complex of antibiotics contains corresponding 7-deoxy- and 7,8,9,10-bisanhydroanthracyclinones.


Asunto(s)
Antibióticos Antineoplásicos/biosíntesis , Streptomyces/metabolismo , Antibióticos Antineoplásicos/análisis , Fenómenos Químicos , Química , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Espectrometría de Masas , Conformación Molecular
15.
Bioorg Khim ; 15(2): 277-80, 1989 Feb.
Artículo en Ruso | MEDLINE | ID: mdl-2500939

RESUMEN

Anthracycline antibiotics (daunorubicin, carminomycin and doxorubicin) N-acylated with antibiotic bruneomycin (streptonigrin) have been obtained from the parent compounds upon treatment with N, N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide. These "chimeric" antibiotics are less active both in vitro and in vivo than the parent antibiotics. This demonstrates the stability of the intermolecular amide linkage in these compounds towards chemical and enzymatic hydrolysis as well as their inability to interact with corresponding receptors in contrast to less hindered derivatives of the parent antibiotics.


Asunto(s)
Carubicina/metabolismo , Daunorrubicina/análogos & derivados , Daunorrubicina/metabolismo , Doxorrubicina/metabolismo , Estreptonigrina/metabolismo , Acilación , Bacillus subtilis/efectos de los fármacos , Carubicina/farmacología , Fenómenos Químicos , Química , Daunorrubicina/farmacología , Diciclohexilcarbodiimida , Doxorrubicina/farmacología , Espectroscopía de Resonancia Magnética , Succinimidas
16.
Antibiot Khimioter ; 33(4): 257-62, 1988 Apr.
Artículo en Ruso | MEDLINE | ID: mdl-3389953

RESUMEN

Structure of galtamycin, a novel anthracycline antibiotic was assessed with 1H NMR, 13C NMR and mass spectroscopy. Galtamycin includes an unusual aglycone i.e. galtamycinone containing the C-glycoside bond and glycosylated with trisaccharide consisting of two fragments of L-rodinose and one fragment of D-olivose.


Asunto(s)
Antraciclinas , Antibióticos Antineoplásicos , Glicósidos , Naftacenos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas
17.
Bioorg Khim ; 13(7): 934-9, 1987 Jul.
Artículo en Ruso | MEDLINE | ID: mdl-3675641

RESUMEN

Alkylation of 2,4-bis-O-(trimethylsilyl)uracil with hexafluoroacetone trifluoroacetylimine gave 5-(2-trifluoroacelylaminohexafluoroprop-2-yl)uracil, which was transformed by alkaline hydrolysis to 5-(2-aminohexafluoroprop-2-yl)uracil. The latter was glycosytated with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-ribofyranosyl chloride by means of various modifications of the silyl method leading to the predominant formation of beta-deoxynucleoside; after deacylation 1-(2-deoxy-beta-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ura cil was obtained. Interaction of silylated 5-(2-trifluoroacetylaminohexafluoroprop-2-yl)uracil with acylgalogenose gave anomeric O-substitutet deoxynucleosides, which were deblocked to give 5-(2-trifluoroacetylaminohexafluoroprop-2-yl)-2'-deoxyuridine and corresponding alpha-anomer. Alkaline hydrolysis of N-trifluoroacetyl group in both individual anomers produced 1-(2-deoxy-alpha-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ur acil and the abovementioned beta-anomer. Of all compounds synthesised only 1-(2-deoxy-beta-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ura cil has a moderate inhibitory effect on replication of vaccinia virus in vitro.


Asunto(s)
Antimetabolitos/síntesis química , Desoxiuridina/análogos & derivados , Alquilación , Antimetabolitos Antineoplásicos/síntesis química , Antivirales/síntesis química , Fenómenos Químicos , Química , Desoxiuridina/síntesis química , Desoxiuridina/farmacología
18.
Bioorg Khim ; 13(4): 539-45, 1987 Apr.
Artículo en Ruso | MEDLINE | ID: mdl-3606674

RESUMEN

New derivatives of 2-C-/(indolyl-3)methyl/-beta-L-threo-L-glycero-3-hexulofuranosono- 1,4-lactone, vis. 1'-ethylascorbigen, 1'-benzylascorbigen and 1',2'-dimethyl-5'-methoxyascorbigen were obtained. In aquous solutions at physiological temperature and pH values ascorbigens disintegrate rather rapidly to yield L-ascorbic acid, the rate of the latter's formation depending on the substituent in the indole nucleus and increasing with growth of pH and temperature. Intraperitoneal injection of 1'-methylascorbigen to mice leads to steady rise of L-ascorbic acid level in blood plasma.


Asunto(s)
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/administración & dosificación , Indoles/síntesis química , Animales , Ácido Ascórbico/sangre , Ácido Ascórbico/síntesis química , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacología , Fenómenos Químicos , Química , Preparaciones de Acción Retardada , Indoles/metabolismo , Indoles/farmacología , Cinética , Espectroscopía de Resonancia Magnética , Ratones
19.
Bioorg Khim ; 11(9): 1248-52, 1985 Sep.
Artículo en Ruso | MEDLINE | ID: mdl-2998405

RESUMEN

Glycosylation of silylated 5-trimethylgermyluracil with 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribofuranosylchloride in dichloroethane in the presence of SnCl4 and subsequent deacylation led to anomeric 5-trimethylgermyl-2'-deoxyuridines. The alpha-nucleoside inhibits HSV-1 replication in vitro, blocks 2'-deoxyuridine incorporation into DNA of hepatoma 22A cells and incorporation of thymidine into DNA of cancer ovarian cells as well. Treatment with 125 mg/kg X 5 days of alpha-nucleoside fails to increase the life-span of mice with leukemia P388.


Asunto(s)
Antineoplásicos/síntesis química , Antivirales/síntesis química , Desoxiuridina/análogos & derivados , Animales , Células Cultivadas , Fenómenos Químicos , Química , Pollos , ADN de Neoplasias/biosíntesis , Desoxiuridina/síntesis química , Desoxiuridina/farmacología , Fibroblastos/microbiología , Germanio/farmacología , Neoplasias Hepáticas Experimentales/metabolismo , Ratas , Simplexvirus/fisiología , Replicación Viral/efectos de los fármacos
20.
Bioorg Khim ; 10(12): 1645-54, 1984 Dec.
Artículo en Ruso | MEDLINE | ID: mdl-6543305

RESUMEN

Glycosylation of 5-trimethylsilyl- and 5-triethylsilyluracil as well as 5-trimethylsilylcytosine with 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribofuranosylchloride and subsequent deacylation led to alpha- and beta-anomers of 5-Me3SidUrd, 5-Et3SidUrd and 5-Me3SidCyd. 1-(alpha-D-Arabinofuranosyl)-5-trimethylsilyluracil was synthesized starting from the derivatives of 2,3,5-tri-O-benzoyl-D-arabinofuranose and then converted to alpha-5-Me3SidUrd via 1-(2,2'-anhydro-alpha-D-ribofuranosyl)-5-trimethylsilyluracil and 1-(2-chloro-2-deoxy-alpha-D-arabinofuranosyl)-5-trimethylsilyluracil+ ++. Out of all synthesized compounds, only alpha-5-Me3SidUrd inhibits the replication of HSV-1 both in vitro and in vivo; it also exerts a pronounced therapeutic effect in guinea pigs with herpes genitalis induced by HSV-2. The resistance of alpha-5-Me3SidUrd to pyrimidine phosphorylases facilitates its antiviral activity in vivo.


Asunto(s)
Encefalitis/tratamiento farmacológico , Herpes Genital/tratamiento farmacológico , Herpes Simple/tratamiento farmacológico , Nucleósidos de Pirimidina/síntesis química , Silicio/síntesis química , Compuestos de Trimetilsililo/síntesis química , Animales , Fenómenos Químicos , Química , Encefalitis/etiología , Femenino , Cobayas , Masculino , Nucleósidos de Pirimidina/uso terapéutico , Ratas , Compuestos de Trimetilsililo/uso terapéutico
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