Toxicity, metabolism, DNA incorporation with lack of repair, and lactate production for 1-(2′-fluoro-2′-deoxy-β-D-arabinofuranosyl)-5-iodouracil in U-937 and MOLT-4 cells was written by Klecker, Raymond W.; Katki, Aspandiar; Collins, Jerry M.. And the article was included in Molecular Pharmacology on December 31,1994.Synthetic Route of C10H13FN2O5 The following contents are mentioned in the article:
Two cell lines, U-937 and MOLT-4, were used to investigate the toxicity, DNA incorporation, and effect on mitochondria of 1-(2′-fluoro-2′-deoxy-β-D-arabinofuranosyl)-5-iodouracil (FIAU) and its putative metabolite 1-(2′-fluoro-2′-deoxy-β-D-arabinofuranosyl)uracil (FAU). After 72-h incubation, the IC50 values for FIAU were 6.4 μM for U-937 cells and 26 μM for MOLT-4 cells. IC50 values for FAU were 10-fold higher in both cell lines. Incubation for 24 h with 10 μM [2-14C]FIAU led to 2.1% and 0.93% replacement of thymidine in DNA of U-937 and MOLT-4 cells, resp. The predominant radioactive species measurable in DNA was FIAU. A similar incubation with [2-14C]FAU resulted in 4-fold lower DNA incorporation of a single radioactive species that coeluted with 1-(2′-fluoro-2′-deoxy-β-D-arabinofuranosyl)-5-methyluracil (FMAU). There was no evidence of a selective repair process after DNA incorporation of FIAU or FAU (FMAU). Increased intracellular concentrations of FIAU triphosphate and incorporation into DNA were associated with an increase in cellular toxicity. Continuous exposure to a clin. achievable concentration of FIAU, 0.44 μM, produced a constant DNA incorporation of 0.80% and 0.11% for U-937 and MOLT-4 cells, resp. FIAU was not readily metabolized to FAU or iodouracil by human liver in vitro. Compared with 2′,3′-dideoxycytidine as a pos. control, after 12 days of continuous exposure of U-937 and MOLT-4 cells to FIAU there was no evidence of increased lactate production These data negate several possible mechanisms of FIAU hepatotoxicity(DNA chain termination, DNA polymerase inhibition, one form of selective mitochondrial poisoning, and FAU-mediated toxicity) and provide clues for possible other mechanisms (FIAU triphosphate concentration and DNA incorporation). Further work is needed to develop a complete explanation for the delayed hepatic toxicity observed in the investigational clin. trials of FIAU. This study involved multiple reactions and reactants, such as 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3Synthetic Route of C10H13FN2O5).
1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Synthetic Route of C10H13FN2O5
69256-17-3;1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione;The future of 69256-17-3;New trend of C10H13FN2O5;function of 69256-17-3