title: Synthesis, characterization, and in vitro assay of folic acid conjugates of 3'-azido-3'-deoxythymidine (AZT): toward targeted AZT based anticancer therapeutics.
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 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.
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY 13208-4100, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Vortherms
authors.forename: Robert P
authors.initials: RP
authors.lastname: Doyle
authors.forename: Dayuan
authors.initials: D
authors.lastname: Gao
authors.forename: Olivia
authors.initials: O
authors.lastname: Debrah
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
mesh_terms: 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*
chemical_list: D002352:Carrier Proteins; D003603:Cytotoxins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D015215:Zidovudine; D005492:Folic Acid