Cytidine 6-azacytidine

The UV spectra of azacytidine are similar to those of uridine and 6-azauridine but differ from those of cytosine and cytidine. On the other hand, the spectrum of the 4-dimethylamino derivative is different from that of 6-azacytidine and similar to that of cytidine. "... 

The IR spectra of chloroform solutions of 6-azacytidine and its derivatives show that these compounds, like the corresponding cytidine derivatives, exist in the amino form. ... 

An important difference between the two compounds is that azacytidine (2) incorporates into RNA, while decitabine (1) acts on DNA. Within cells, decitabine (1) is phosphorylated by deoxycytidine kinase, and after conversion to decitabine triphosphate, it is incorporated into DNA in place of deoxycytidine triphosphate. Azacitidine (2) is phosphorylated by uridine-cytidine kinase and eventually incorporated into RNA, inhibiting the processing of ribosomal RNA and ultimately protein synthesis. Azacitidine (2) can also inhibit DNMTs when azacytidine diphophate is reduced to decitabine diphosphate, which is further phosporylated by kinases to dcitabine triphosphate and incorporated into DNA. Because of the inefficiency of these extra steps, the hypomethylating potency of 2 is believed to be one fifth to one tenth that of l.6-8... 

Azacytidine was approved in 2004 for the treatment of patients with myelodysplastic syndrome, a disorder of hematopoietic cell maturation that can progress to acute leukemia. Azacytidine, a cytidine nucleoside analog, causes hypomethylation of DNA. Hypomethylation may normalize the function of genes that control cell differentiation and proliferation, promoting normal cell maturation. ... 

Azacytidine, although of somewhat limited clinical utility, is fascinating from a biochemical standpoint. There are reports that this drug is deaminated by cytidine deaminase in bacteria and possibly humans, yet 5-fluorocytosine, which is antifungal because of deamination to 5-fluororuacil, is susceptible fungal cells, is selectively nontoxic in humans... 

Methylation occurs after replication and unmethylated sites in parental DNA remain unmethylated in daughter DNA. 5-Azacytidine, a cytidine analog that is metabolized like cytidine to the analog of dCTP (but cannot be methylated), can be incorporated into DNA. After replication replaces the modified C with a real C, it too remains unmethylated (see Figure 25.3b). 

Azacytidine is an analog of cytidine in which the carbon at position 5 of the pyrimidine ring has been replaced by a nitrogen. Azacytidine is phosphorylated by cells and incorporated into DNA just like cytidine, but azacytidine cannot be methylated at position 5, the sole site of eukaryotic DNA methylation. 

Interestingly, after the cells treated with azacytidine are allowed to replicate so as to replace the azacytidine residues with cytidine residues, the newly replicated sequences remain unmethylated, even if they were methylated prior to azacytidine treatment. 

Azacytidine Streptoverticillus lakadamus Azacytosine Ribose Cytidine... 

There have been many reports of syntheses of deoxy nucleosides by standard sugar-base condensation reactions. These include 5 -deoxy-ribo nucleosides and 5 -mono- or 5",5-di-deuterated analogues, as well as derivatives of 5-deoxy-D-xylose and 5-deoxy-D-glucose, 5-alkylated thymidine derivatives, 2 -deoxy-6-methyl-5-azacytidine and its a-anomer, the thymidine analogue 4-(2-deoxy-B-D-erythro-pento-furanosyl)-6-methyl-l,2,4-triazine 3(HH)-one-1-oxide, 6-aza-3-deaza analogues of 2 -deoxy-cytidine and 2 -deoxyuridine,3 -deoxycytidine from a 3-deoxy-ribofuranose obtained from a fermentation broth producing the 3 -deoxy nucleoside antibiotic, cordycepin, 4-deoxy-DL-threo-pentopyranosyl pyrimidine nucleosides, and 5 -C-methyluridines derived from 6-deoxy-D-allose and 6-deoxy-D-talose. A range... 

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