Summary
Arabinosyl-5-azacytosine (ara-AC) is a new compound which combines the structural characteristics of arabinosyl cytosine (ara-C) and 5-azacytidine (5-AC). These three compounds, injected intraperitoneally, were evaluated in direct comparison against the intracerebral L1210 leukemia model. 5-AC was active in a non-schedule dependent manner producing increase in life span (ILS) values of 70%. The effects of both araC and ara-AC were schedule-dependent with the best activity (ILS ca. 600%; multiple long term survivors) observed using an around-the-clock treatment schedule. In all experiments, ara-AC appeared to be more efficacious than ara-C. In some instances, ara-AC was as active as the positive control compound, BCNU. Excellent activity for ara-AC was also observed against the intracerebral P388 leukemia system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beisler JA, Abbasi MM, Driscoll JS: Synthesis and antitumor activity of 5-azacytosine arabinoside. J Med Chem 22:1230–1234, 1979
Beisler JA, Abbassi MM, Driscoll JS: The synthesis and antitumor activity of arabinosyl-5- azacytosine. Biochem Pharmacol 26:2469–2472, 1977
Driscoll JS: The preclinical new drug research program of the National Cancer Institute. Cancer Treat Rep 68:63–76, 1984
Kline I, Venditti JM, Tyrer DD, Mantel N, Goldin A: Chemotherapy of leukemia L1210 in mice with 1-β-D-arabinofuranosylcytosine hydrochloride. II. Effectiveness against intracerebrally and subcutaneously inoculated leukemic cells. Cancer Res 26 Part 1:1930–1937, 1966
Chabot GG, Momparler RL: Antileukemic activity of 5-aza- 2′-deoxytidine and cytarabine against intracerebral L1210 murine leukemia. Cancer Treat Rept 68:1483–1487, 1984
Peng GW, Marquez VE and Driscoll JS: Potential central nervous system antitumor agents. Hydantoin derivatives. J Med Chem 18:846–849, 1975
Driscoll JS, Dudeck L, Congleton G, Geran RI: Potential CNS antitumor agents VI. Aziridinylbenzoquinones III. J Pharm Sci 68:185–188, 1979
Geran RI, Greenberg NH, Macdonald MM, Schumacher AM, Abbott BJ: Protocols for screening chemical agents and natural products against animal tumors and other biological systems (third edition). Cancer Chemother Rept (Part 3) 3:1–103, 1972
Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute: In vivo cancer models 1976–1982. NIH Publication No. 84-2635, p. 16, February 1984
Fulton DS, Levin VA, Gutin PH, Edwards MSB, Seager ML, Stewart J, Wilson CB: Intrathecal cytosine arabinoside for the treatment of meningeal metastases from malignant brain tumors and systemic tumors. Cancer Chemother Pharmacol 8:285–291, 1982
Zimm S, Collins JM, Miser J, Chatterji D, Poplack DG: Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharmacol Ther 35:826–830, 1984
Dion RL, Jayaram HN, Cooney DA, Ahluwalia GS, Johns DG: Studies on the mode of action of 1-β-D-arabinofuranosyl-5-azacytosine (NSC-281272). Proc Am Assoc Cancer Res 24:297, 1983
Townsend A, Leclerc J-M, Bouchard J, Cheng YC and Cooney D: The biochemical pharmacology of 5-aza-I-β-D-arabinofuranosylcytosine (5-ara-AC), a new antitumor compound. Fed Proc 43:1534, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Driscoll, J.S., Johns, D.G. & Plowman, J. Comparison of the activity of Arabinosyl-5-azacytosine, Arabinosyl cytosine, and 5-azacytidine against intracerebrally implanted L1210 leukemia. Invest New Drugs 3, 331–334 (1985). https://doi.org/10.1007/BF00170754
Issue Date:
DOI: https://doi.org/10.1007/BF00170754