Abstract |
The antitumor activity and toxicity of two new 1-beta-D-arabinofuranosyl-cytosine ( ara-C) conjugates of cortisol and corticosterone linked through a phosphodiester bond between the 5' and 21 positions of the respective moieties ( cortisol- and corticosterone-p- ara-C) were investigated in L1210 lymphoid leukemia cells in mice. They are highly active against both i.p.- and i.c.-implanted ara-C-sensitive lymphoid leukemia in mice, exceeding the activity produced by the parent drug, ara-C. For example, corticosterone-p- ara-C exhibited the respective ILS values of 306% at 50 mg/kg/day X 9 and 294% at 75 mg/kg/day X 9 on survivals of i.p.- and i.c.-inoculated L1210 leukemic mice. The effectiveness of the conjugates seems to depend on schedules of the treatments. The 9-day continuous treatments showed a better therapeutic effectiveness than those with either a 5-day, a single or a widely spaced (q 4d., 1, 5, 9) treatment. However, they were found to be marginally effective against i.p.-implanted ara-C-resistant L1210 leukemia in mice. They were also inhibitory against proliferation of human leukemia-lymphoid cells in culture. Their superior antitumor activity and resistance to cytidine deaminase suggests that they serve as a prodrug form of ara-C or ara- CMP.
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Authors | C I Hong, A Nechaev, A J Kirisits, D J Buchheit, C R West |
Journal | European journal of cancer & clinical oncology
(Eur J Cancer Clin Oncol)
Vol. 19
Issue 8
Pg. 1105-12
(Aug 1983)
ISSN: 0277-5379 [Print] England |
PMID | 6684555
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cytarabine
- cortisol-4-ara-C
- cortisone-4-ara-C
- Cortisone
- Hydrocortisone
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Topics |
- Animals
- Cell Division
(drug effects)
- Cell Line
- Cortisone
(analogs & derivatives, therapeutic use)
- Cytarabine
(analogs & derivatives, therapeutic use)
- Dose-Response Relationship, Drug
- Female
- Humans
- Hydrocortisone
(analogs & derivatives, therapeutic use)
- Leukemia L1210
(drug therapy)
- Lymphocytes
(drug effects)
- Mice
- Mice, Inbred Strains
- Neoplasm Transplantation
- Peritoneum
- Skull
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