Eriksson, Staffan
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
Abstract
Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase I in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues. (C) 2004 Elsevier Ltd. All rights reserved.
Keywords
thymidine kinase 1; nido-carborane; closo-carborane; boron neutron capture therapy
Published in
Applied Radiation and Isotopes
2004, volume: 61, number: 5, pages: 1125-1130
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
SLU Authors
UKÄ Subject classification
Organic Chemistry
Publication identifier
- DOI: https://doi.org/10.1016/j.apradiso.2004.05.023
Permanent link to this page (URI)
https://res.slu.se/id/publ/3558