5-chloro-2 -deoxycytidine

Another mechanism of myeloperoxidase-initiated DNA damage by neutrophils has been proposed by Henderson et al. [47]. These authors showed that the myeloperoxidase/hydrogen peroxide/chloride system catalyzed the chlorination of 2 -deoxycytidine into 5-chloro-2 -deoxycytidine. As HOC1 is unable to react with 2 -deoxycytidine in the absence of Cl-, it was concluded that in this case a genuine active intermediate was molecular chlorine formed by Reactions (2) and (3) ... 

Furthermore, it was found that stimulated human neutrophils are able to produce 5-chloro-2 -deoxycytidine and that the myeloperoxidase system generates just the same levels of 5-chlorocytosine in DNA and RNA in vitro (Reaction (4), Figure 28.3). It is possible that myeloperoxidase-generated chlorinated products may modify nuclear acids of pathogens and nuclear acids in host cells during inflammation. Hawkins et al. [48] suggested that DNA oxidation may be initiated by protein chloramines formed in the reaction of HOCl with histones in the nucleosome. 

Furthermore, it was found that stimulated human neutrophils are able to produce 5-chloro-2 -deoxycytidine and that the myeloperoxidase system generates just the same levels of... 

S -Chloro- -deoxycytidine B -Phosphate 2 -Chloro-2 -deoxycytidine 6 -Monophosphate... 

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

Deoxycytidine was fully acylated with anisoyl chloride in pyridine to (117), and this was converted into A -anisoyl-2 -deoxycytidine (118). The mono-O-acyl derivative was treated with chloro-bis(p-methoxyphenyl)-phenylmethane (119) in pyridine, to yield 120, which was phosphorylated with 2-cyanoethyl phosphate and (65) in pyridine to the phospho-diester (121) in high yield. Removal of the protecting groups was achieved in two ways. One method involved the treatment of (121) with aqueous ammonia to give (122) which, on treatment with 80% acetic acid at room temperature for twenty minutes, afforded 2 -deoxycytidine 3 -phosphate... 

Leegwater, P.A., De Abreu, R.A., and Albertioni, F., Analysis of DNA methylation of the 5 region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2-arabino-fluoro-2 -deoxyadenosine (CAFdA)-resistant ceU, Cancer Lett., 130 (1-2), 169-173,1998. 

Chloro-2 -deoxycytidine (0.5 mmole) is dissolved in triethylphos-phate (2 ml) and cooled to 0° redistilled phosphoryl chloride (0.3 ml), also cooled to the same temperature, is added. The reaction mixture is... 

Azido and 3 -amino analogues of 2 -deoxy-5-substituted uridine and cytidine, together with 3 -amino-5 -fluoro-thymidine, have been prepared by standard procedures using 3 -0-mesyl ester intermediates the most active anti-cancer compounds were the 3 -amino-5-fluoro analogues of 2 -deoxyuridine and 2 -deoxycytidine cuid the 3 -amino analogue of 2 -deoxycytidine.An alternative doubleinversion sequence at C-3 using a 3 -chloro-3 -deoxyxylo-nucleo-side intermediate has been described for the preparation of 3 -... 

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