Eriksson, Staffan
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
3-[5-{2-(2,3-Dihydroxyprop-1-yl)-o-carboran-1-yl} pentan-1-yl] thymidine (compound 1, N5-2OH) belongs to a novel class of boron delivery agents for neutron capture therapy, which was designated 3-carboranylthymidine analogue (3CTAs). Two shorter and more convenient synthetic routes were developed for the synthesis of 1 in the B-10-enriched form, which is necessary for its preclinical and clinical evaluation in neutron irradiation studies. For more insight on structure-activity relationships, various stereochemical and geometrical isomers of 1 were synthesized and their specificities as substrate for human thymidine kinase 1 (hTK1) were evaluated. A computational model for the binding of various isomers of 1 to the active site of hTK1 was developed. Preliminary studies carried out in F98 glioma bearing rats that had received a B-10-enriched form of 1 followed by neutron irradiation demonstrated a significant prolongation in survival times compared to control animals, suggesting that further studies are warranted to evaluate the therapeutic potential of 1.
Published in
Journal of Medicinal Chemistry
2006, volume: 49, number: 18, pages: 5513-5523
Publisher: AMER CHEMICAL SOC
SLU Authors
UKÄ Subject classification
Animal and Dairy Science
Veterinary Science
Publication identifier
- DOI: https://doi.org/10.1021/jm060413w
Permanent link to this page (URI)
https://res.slu.se/id/publ/11230