Detail of "10299-44-2"

Reference

Metabolism and metabolic effects of 8-azainosine and 8-azaadenosine

Metabolism and metabolic effects of 8-azainosine and 8-azaadenosine. Bennett, L. Lee, Jr.; Allan, Paula W. (Kettering-Meyer Lab., South. Res. Inst., Birmingham, Ala., USA). Cancer Res., 36(11, Pt. 1), 3917-23 (English) 1976. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Metabolic studies in cell cultures were performed with 8-azainosine (I) [4968-68-7] and with the structurally related nucleoside, 8-azaadenosine (II) [10299-44-2], which has a lower degree of antitumor activity than does I. In H. Ep. 2 cells and in Ca775 cells, both 14C-labeled nucleosides were metabolized to nucleotides of 8-azaadenine (8-aza-A) [1123-54-2] and 8-azaguanine (8-aza-G) [134-58-7] and incorporated into polynucleotides as 8-aza-A and 8-aza-G. I was incorporated primarily as 8-aza-G, whereas II was incorporated about equally as 8-aza-A and 8-aza-G. In H. Ep. 2 cells, the extent of incorporation of I as 8-aza-G was about one-half that found when [14C]-8-aza-G was the precursor. In the H. Ep. 2/Fa/FAR cell line, II and I were metabolized similarly, in that both were incorporated into polynucleotides principally as 8-aza-G; apparently, in this cell line which is deficient in adenosine kinase [9027-72-9] and adenine phosphoribosyltransferase [9027-80-9], II is metabolized by conversion to I. A cell line (H. Ep. 2/I), which was resistant to I but sensitive to II and which retained hypoxanthine (guanine)-phosphoribosyltransferase activity, metabolized I to only a small extent. However, in this cell-line, II was more extensively metabolized and was incorporated primarily as 8-aza-A. The failure of these cells to convert II or I to 8-aza-G indicates that the basis for resistance may be a change in the substrate specificities of the enzymes of guanosine monophosphate synthesis such that these cells no longer effectively convert 8-azainosine monophosphate to 8-azaguanosine monophosphate.There are some commonly used reagents with their cas registry numbers 65-86-1 and 9027-80-9 in this article. II was a potent inhibitor of purine synthesis de novo, but I, at concns. much higher than the inhibitory concn. of II, did not inhibit this process. In H. Ep. 2 cells, I blocked the conversion of orotic acid [65-86-1] to uridine nucleotides and caused an accumulation of orotidine [314-50-1]. This inhibition of pyrimidine biosynthesis apparently does not contribute significantly to the cytotoxicity of I because uridine provided no degree of reversal of its inhibition of the growth of cell cultures. .