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.
Original language | English |
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Pages (from-to) | 1125-1130 |
Number of pages | 6 |
Journal | Applied Radiation and Isotopes |
Volume | 61 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Nov 2004 |
Keywords
- BNCT
- Boc
- Boron neutron capture therapy
- Closo-carborane
- High resolution mass spectrometry
- HRMS
- Monophosphate
- MP
- N-tert-Butoxycarbonyl
- Nido-carborane
- NMR
- Nuclear magnetic resonance
- Reversed phase
- RP
- TBAF
- Thymidine kinase 1