Sensitivity of some arabinosylcytosine derivatives to enzymatic deamination by cytidine deaminase from mouse kidney

1982 ◽  
Vol 47 (10) ◽  
pp. 2824-2830 ◽  
Author(s):  
Jindřich Kára ◽  
Markyta Bártová ◽  
Miloš Ryba ◽  
Hubert Hřebabecký ◽  
Josef Brokeš ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Nucleoside Analogs ◽  
Mouse Kidney ◽  
Derivatives Of ◽  
Uracil Derivative

Enzymatic deamination of derivatives of arabinosylcytosine by partially purified cytidine deaminase isolated from mouse kidney is studied. The rate of deamination of 5'-chloroarabinosylcytosine (Ia), 5'-bromoarabinosylcytosine (Ib), 5'-chlorocyclocytidine (II), and 2',5'-anhydroarabinosylcytosine (III) is compared with that of arabinosylcytosine, of its N4-acetyl-, tri-O-acetyl-, tetraacetyl derivatives and of cyclocytidine. The deamination of the anhydro derivative III to the corresponding uracil derivative IV proceeds significantly slower than that of arabinosylcytosine, and comparably to that of cyclocytidine. The deamination of the 5'-halogeno derivatives Ia, Ib and II proceeds via the anhydro derivative III to IV. Some of the known arabinosylcytosine derivatives, cyclocytidine, N4-acetyl-, tetraacetyl- and tri-O-acetyl derivatives, show a resistance to enzymatic deamination. Different nucleoside analogs are tested as inhibitors of deaminase; only 2-β-D-ribofuranosyl-1,2,4-triazol-3-one possesses some activity.

scholarly journals Mouse Kidney Cytidine Deaminase

1968 ◽  
Vol 243 (10) ◽  
pp. 2534-2537
Author(s):  
R Tomchick ◽  
L D Saslaw ◽  
V S Waravdekar
Keyword(s):  
Cytidine Deaminase ◽  
Mouse Kidney

Preparation of the 1-(2,5-anhydro-β-d-arabinofuranosyl) derivatives of cytosine and uracil and their cleavage with hydrogen bromide

1982 ◽  
Vol 47 (11) ◽  
pp. 2961-2968 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Josef Brokeš ◽  
Jiří Beránek
Keyword(s):  
Aqueous Solution ◽  
Sodium Hydroxide ◽  
Hydrogen Bromide ◽  
Ion Exchanger ◽  
Alternative Synthesis ◽  
Derivatives Of ◽  
Uracil Derivative

Anhydronucleoside Ia was prepared from chloroarabinofuranosylcytosine IIIc or from 2,2'-anhydro-1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)cytosine by the action of a strongly basic ion exchanger. The anhydro derivative IIa was prepared from 2,2'-anhydro-1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)uracil by treatment with aqueous solution of sodium hydroxide. The action of hydrogen bromide in dimethylformamide on 2',5'-anhydronucleosides Ia and IIa leads both to the cleavage of the anhydro bond under formation of the 5'-bromo derivatives IIIa and IVa and to the cleavage of nucleosidic bond. In case of the uracil derivative IIa, the α-arabinofuranosyl derivative V was also isolated after preceding acetylation. For unambiguous proof of the structure, an alternative synthesis of compound V was performed.

Inhibition of Cytidine Deaminase by Derivatives of 1-(β-D-Ribofuranosyl)-Dihydropyrimidin-2-One (Zebularine)

1992 ◽  
Vol 11 (10) ◽  
pp. 1781-1793 ◽  
Author(s):  
Joseph J. Barchi ◽  
Alberto Haces ◽  
Victor E. Marquez ◽  
John J. McCormack
Keyword(s):  
Cytidine Deaminase ◽  
Derivatives Of

Synthesis and biological activity of nucleoside analogs involving modifications in the carbohydrate ring

1985 ◽  
Vol 63 (8) ◽  
pp. 2149-2161 ◽  
Author(s):  
Walter A. Szarek ◽  
B. Mario Pinto ◽  
Masaharu Iwakawa
Keyword(s):  
Biological Activity ◽  
Cell Growth ◽  
Antitumor Activity ◽  
Nucleoside Analogs ◽  
Hela Cell Line ◽  
Biological Screening ◽  
Naturally Occurring ◽  
Derivatives Of ◽  
Substituted 1

The synthesis of a variety of nucleoside analogs involving modifications in the carbohydrate ring is described. In particular, 6-substituted purin-9-yl derivatives of 1-oxa-4-thiacyclohexane and 1,4-dioxacyclohexane have been synthesized. A number of 6-chloropurin-9-yl derivatives of substituted 1-oxa-4-thiacyclohexane have also been derived from the parent compounds by way of a Pummerer rearrangement. A route to nucleoside analogs of 1-oxa-4-thiacyclohexane from naturally occurring nucleosides is illustrated for the case of inosine. A route to nucleoside analogs in which the carbohydrate moiety is replaced by an acyclic moiety bearing α,β-unsaturated esters is also illustrated for the case of uridine. The results of biological screening of these analogs and others previously synthesized in our program against leukemia L-1210 cells in vitro are presented; some of these compounds showed marginal antitumor activity. The screening results of selected compounds against the human HeLa cell line in vitro are also presented; none of the compounds that were tested showed significant inhibitory activity of cell growth.

Haloanilino Derivatives of Pyrimidines, Purines, and Purine Nucleoside Analogs: Synthesis and Activity against Human Cytomegalovirus

1995 ◽  
Vol 38 (10) ◽  
pp. 1811-1819 ◽  
Author(s):  
Maria Medveczky ◽  
Te-Fang Yang ◽  
Joseph Gambino ◽  
Peter Medveczky ◽  
George E. Wright
Keyword(s):  
Human Cytomegalovirus ◽  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Derivatives Of

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA II. Racemic cis-Configured Derivatives

1996 ◽  
Vol 61 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Nucleoside Analogs ◽  
Mitsunobu Reaction ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic N-(cis-2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phosphonates is based on the reaction of cis-2-hydroxycycloalkyl derivatives of protected nucleobases with diisopropyl tosyloxymethanephosphonate. The starting purine-containing nucleoside analogs 5a-5f were prepared by the Mitsunobu reaction of protected nucleobases with trans-2-benzyloxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g-5k were obtained by configurational inversion at C-2' of the corresponding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of their 2,2'-anhydro derivatives.

scholarly journals Selection of drug-resistant transduced cells with cytosine nucleoside analogs using the human cytidine deaminase gene

2001 ◽  
Vol 8 (9) ◽  
pp. 669-676 ◽  
Author(s):  
Christian M Beauséjour ◽  
Nicoletta Eliopoulos ◽  
Louise Momparler ◽  
Ngoc Loan Oanh Le ◽  
Richard L Momparler
Keyword(s):  
Cytidine Deaminase ◽  
Nucleoside Analogs ◽  
Drug Resistant ◽  
Selection Of

scholarly journals Synergistic Antimicrobial Activities of Folic Acid Antagonists and Nucleoside Analogs

2009 ◽  
Vol 54 (3) ◽  
pp. 1226-1231 ◽  
Author(s):  
Johannes Zander ◽  
Silke Besier ◽  
Hanns Ackermann ◽  
Thomas A. Wichelhaus
Keyword(s):  
Folic Acid ◽  
Nucleoside Analogs ◽  
Bactericidal Effect ◽  
Antimicrobial Activities ◽  
Nucleoside Analog ◽  
Folic Acid Antagonists ◽  
Bacterial Utilization ◽  
Time Kill ◽  
Derivatives Of

ABSTRACT The antimicrobial activities of folic acid antagonists are supposed to be antagonized by elevated extracellular thymidine concentrations in damaged host tissues. Therefore, this study was aimed at screening for nucleoside analogs that impair bacterial thymidine utilization and analyzing the combined antimicrobial activities of nucleoside analogs and folic acid antagonists in the presence of thymidine. Our screening results revealed that different nucleoside analogs, in particular halogenated derivatives of 2′-deoxyuridine, substantially impaired the bacterial utilization of extracellular thymidine in Staphylococcus aureus. Time-kill methods showed that 5-iodo-2′-deoxyuridine enhanced the extent of killing of trimethoprim-sulfamethoxazole (SXT) at 24 h against S. aureus in the presence of thymidine (200 μg/liter). While SXT (40 mg/liter) alone did not kill bacteria in the presence of thymidine, its combination with the nucleoside analog at a concentration of 8 μmol/liter showed a bactericidal effect. Moreover, 5-iodo-2′-deoxyuridine combined with SXT in the presence of thymidine showed a broad spectrum of activity against several Gram-positive and Gram-negative bacteria. In conclusion, these data provide evidence that the in vitro antimicrobial activity of SXT in the presence of thymidine can be significantly improved by combination with a nucleoside analog.

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