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Nucleosides, Nucleotides & Nucleic Acids Volume 20, 2001 - Issue 4-7
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Original Articles

SYNTHESIS AND BIOLOGICAL EVALUATION OF BORONATED NUCLEOSIDES FOR BORON NEUTRON CAPTURE THERAPY (BNCT) OF CANCER

W. Tjarks The Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio, 43210, U.S.A.Correspondence[email protected]
,
J. Wang Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
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S. Chandra Cornell University, Departmeny of Chemistry and Chemical Biology, Ithaca, New York, U.S.A.
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W. Ji The Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio, 43210, U.S.A.
,
J. Zhuo The Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio, 43210, U.S.A.
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A. J. Lunato The Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio, 43210, U.S.A.
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C. Boyer NewBiotics, Inc., San Diego, California, U.S.A.
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Q. Li NewBiotics, Inc., San Diego, California, U.S.A.
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E. V. Usova Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
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S. Eriksson Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
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G. H. Morrison Cornell University, Departmeny of Chemistry and Chemical Biology, Ithaca, New York, U.S.A.
&
G. Y. Cosquer The Ohio State University, College of Pharmacy, 500 W. 12th Ave, Columbus, Ohio, 43210, U.S.A.
 show all
Pages 695-698 | Published online: 07 Feb 2007
 
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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.

ACKNOWLEDGMENTS

This work was supported by the U.S. Department of Energy grants DE-FG02-90ER60972 and DE-FG02-ER61138, and European Commission grant BMH4-CT96-0479.

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