Synthesis, characterization, and in vitro assay of folic acid conjugates of 3'-azido-3'-deoxythymidine (AZT): toward targeted AZT based anticancer therapeutics.
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 gamma-regioisomer over the inactive alpha-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 approximately 20-fold greater potency against the resistant ovarian line was observed for the conjugates.
Vortherms
Anthony R
AR
Department of Chemistry, Syracuse University, Syracuse, NY 13208-4100, USA.
Doyle
Robert P
RP
Gao
Dayuan
D
Debrah
Olivia
O
Sinko
Patrick J
PJ
D002352:Carrier Proteins / Q000819:agonists; D002460:Cell Line; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance / Q000187:drug effects; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists; D015215:Zidovudine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D002352:Carrier Proteins; D003603:Cytotoxins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D015215:Zidovudine; D005492:Folic Acid