The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position
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 1 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.
- Publication:
-
Applied Radiation and Isotopes
- Pub Date:
- 2004
- DOI:
- 10.1016/j.apradiso.2004.05.023
- Bibcode:
- 2004AppRI..61.1125B
- Keywords:
-
- Thymidine kinase 1;
- Nido-carborane;
- Closo-carborane;
- Boron neutron capture therapy