title: Synthesis and biological evaluation of boronated nucleosides for boron neutron capture therapy (BNCT) of cancer.
abstract: Several N-3 substituted carboranyl Thd analogs were synthesized. These agents as well as some non-boronated nucleosides were evaluated in phosphoryl transfer assays with recombinant human TK1 and TK2. For some carboranyl thymidine analogs, TK1 phosphorylation rates approached 38% that of thymidine. Their in vitro cytotoxicty appeared to correlate with the TK1 levels in the tested cells. In some cases increased uptake in tumor cell nuclei compared with the surrounding cytoplasm was detected in vitro.
authors.affiliation: Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio 43210, USA. tjarks.l@osu.edu
authors.forename: W
authors.initials: W
authors.lastname: Tjarks
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Chandra
authors.forename: W
authors.initials: W
authors.lastname: Ji
authors.forename: J
authors.initials: J
authors.lastname: Zhuo
authors.forename: A J
authors.initials: AJ
authors.lastname: Lunato
authors.forename: C
authors.initials: C
authors.lastname: Boyer
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: E V
authors.initials: EV
authors.lastname: Usova
authors.forename: S
authors.initials: S
authors.lastname: Eriksson
authors.forename: G H
authors.initials: GH
authors.lastname: Morrison
authors.forename: G Y
authors.initials: GY
authors.lastname: Cosquer
mesh_terms: D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy; D005354:Fibrosarcoma / Q000201:enzymology / Q000378:metabolism / Q000532:radiotherapy; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D010766:Phosphorylation; D013347:Subcellular Fractions / Q000378:metabolism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: D001896:Boron Compounds; C105339:thymidine kinase 2; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D013936:Thymidine