Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents

Bhupender S. Chhikara, Deendayal Mandal, Keykavous Parang

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)4601-4608
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume45
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Cytarabine
Leukemia
Esters
Derivatives
Myristic Acid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nucleosides
Acute Myeloid Leukemia
Hydroxyl Radical
Half-Life
Fatty Acids
Plasmas
Acids
Growth

Keywords

  • Cellular uptake
  • Cytarabine
  • Fatty acids
  • Leukemia
  • Nucleoside
  • Prodrug

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents. / Chhikara, Bhupender S.; Mandal, Deendayal; Parang, Keykavous.

In: European Journal of Medicinal Chemistry, Vol. 45, No. 10, 10.2010, p. 4601-4608.

Research output: Contribution to journalArticle

Chhikara, Bhupender S. ; Mandal, Deendayal ; Parang, Keykavous. / Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents. In: European Journal of Medicinal Chemistry. 2010 ; Vol. 45, No. 10. pp. 4601-4608.
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