Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT): Toward targeted AZT based anticancer therapeutics

Anthony R. Vortherms, Robert P. Doyle, Dayuan Gao, Olivia Debrah, Patrick J. Sinko

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Conjugates of three components namely folic acid, poly(ethyleneglycol) and 3 ′-azido-3 ′-deoxythymidine (AZT) are presented. Folate-PEG units were coupled to AZT to facilitate delivery of the nucleoside into the cell. A convenient separation of the polydisperse PEGylated-folic acid regioisomers produced upon conjugation is described. This is to select for the active γ-regioisomer over the inactive α-regioisomer. In vitro cytotoxicity assays were conducted against an ovarian cell line (A2780/AD) that overexpresses the folate receptor (FR) and compared to a FR free control cell line. Compared to AZT a ∼20-fold greater potency against the resistant ovarian line was observed for the conjugates.

Original languageEnglish (US)
Pages (from-to)173-185
Number of pages13
JournalNucleosides, Nucleotides and Nucleic Acids
Volume27
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • 3′-azido-3′-deoxythymidine nucleoside
  • Anticancer agent
  • Folic acid
  • Isomer separation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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