Synthesis and biological effects of 2'-fluoro-5-ethyl-1β-D-arabinofuranosyluracil Journal Article
| Authors: | Chou, T. C.; Kong, X. B.; Fanucchi, M. P.; Cheng, Y. C.; Takahashi, K.; Watanabe, K. A.; Fox, J. J. |
| Article Title: | Synthesis and biological effects of 2'-fluoro-5-ethyl-1β-D-arabinofuranosyluracil |
| Abstract: | 2'-Fluoro-5-ethyl-1-β-D-arabinofuranosyluracil (FEAU) was synthesized, and its biological activities were compared with those of 2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU). Earlier studies indicated that both compounds showed potent anti-herpes simplex virus activity, with a 50% effective dose (ED50) of <0.25 μM. In the present study the cell growth inhibitory activity of FEAU (ED50), 200 to 2,060 μM) was found to be about 100-fold less than that of FMAU. With an ED50 ranging from 630 to 3,700 μM, FEAU only weakly inhibited thymidine incorporation into DNA, as compared with FMAU with an ED50 of 9 to 28 μM. Following exposure to [2-14C]FEAU (100 μM), 0.48 pmol/106 cells per h was incorporated into the DNA of herpes simplex virus type 1-infected Vero cells, whereas no detectable incorporation was found in uninfected Vero cells or L1210 cells. The K(i) of FEAU for thymidine kinase purified from human leukemic cells was > 150 μM. For herpes simplex virus type 1- and 2-encoded thymidine kinases, the K(i)s were 0.6 and 0.74 μM, respectively. Both FEAU and FMAU were relatively nontoxic for mice, with a 50% lethal dose of >800 mg/kg per day (four intraperitoneal doses). However, the lethal dose of FEAU for dogs was 100 mg/kg per day (10 intravenous doses), a dose which is 40- to 80-fold greater than the toxic dose of FMAU. These results suggest that FEAU is a worthy candidate for further development as an antiherpetic agent. |
| Keywords: | in vitro study; drug synthesis; cell culture; herpes virus; thymidine kinase; antivirus agent; virus infection; 5 ethyl 2' fluorouracil arabinoside; virus dna; drug comparison; clevudine; article |
| Journal Title: | Antimicrobial Agents and Chemotherapy |
| Volume: | 31 |
| Issue: | 9 |
| ISSN: | 0066-4804 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1987-09-01 |
| Start Page: | 1355 |
| End Page: | 1358 |
| Language: | English |
| DOI: | 10.1128/aac.31.9.1355 |
| PUBMED: | 2823696 |
| PROVIDER: | scopus |
| PMCID: | PMC174941 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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