Abstract
Cytarabine is a chemotherapeutic agent predominately used for the treatment of acute myeloid leukemia and lymphoblastic leukemia. Cytarabine is a polar nucleoside, has a short plasma half-life, and its use is associated with severe side effects. Fatty acyl derivatives of cytarabine were synthesized with the expectation to improve cellular uptake and generate derivatives with a longer duration of action. Multi-step protection and deprotection reactions of hydroxyl and amino groups and conjugation with a fatty acid (i.e., myristic acid and 12-thioethyldodecanoic acid) afforded 5′-O-substituted, 2′-O-substituted, and 2′,5′-disubstituted fatty acyl derivatives of cytarabine. 2′,5′-Dimyristoyl derivative of cytarabine was found to inhibit the growth of CCRF-CEM cells by approximately 76% at concentration of 1 μM after 96 h incubation.
Original language | English (US) |
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Pages (from-to) | 4601-4608 |
Number of pages | 8 |
Journal | European Journal of Medicinal Chemistry |
Volume | 45 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2010 |
Externally published | Yes |
Keywords
- Cellular uptake
- Cytarabine
- Fatty acids
- Leukemia
- Nucleoside
- Prodrug
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Pharmacology