TY - JOUR
T1 - Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT)
T2 - Toward targeted AZT based anticancer therapeutics
AU - Vortherms, Anthony R.
AU - Doyle, Robert P.
AU - Gao, Dayuan
AU - Debrah, Olivia
AU - Sinko, Patrick J.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - 3′-azido-3′-deoxythymidine nucleoside
KW - Anticancer agent
KW - Folic acid
KW - Isomer separation
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U2 - 10.1080/15257770701795946
DO - 10.1080/15257770701795946
M3 - Article
C2 - 18205071
AN - SCOPUS:38349132026
SN - 1525-7770
VL - 27
SP - 173
EP - 185
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 2
ER -