Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy.
The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O-(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1-ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba-++ +nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o-carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 micrograms/g of cells for the neutral closo structures compared with 1.5 micrograms/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro-closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 micrograms/g of cells.
Tjarks
W
W
College of Pharmacy, Ohio State University, Columbus 43210.
Anisuzzaman
A K
AK
Liu
L
L
Soloway
A H
AH
Barth
R F
RF
Perkins
D J
DJ
Adams
D M
DM
D000818:Animals; D001895:Boron; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009502:Neutrons; D011882:Radiotherapy, High-Energy; D051381:Rats; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D005947:Glucose; D001895:Boron; D014529:Uridine