These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Synthesis and biological evaluation of neutral and zwitterionic 3-carboranyl thymidine analogues for boron neutron capture therapy.
    Author: Byun Y, Yan J, Al-Madhoun AS, Johnsamuel J, Yang W, Barth RF, Eriksson S, Tjarks W.
    Journal: J Med Chem; 2005 Feb 24; 48(4):1188-98. PubMed ID: 15715485.
    Abstract:
    Novel 3-carboranyl thymidine analogues (3CTAs) were synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT). This library includes six zwitterionic NH(3)(+)-nido-m-carborane-substituted thymidine analogues (Thds) and the corresponding neutral NH(2)-closo-m-carborane-substituted counterparts. All compounds of this library were good substrates for recombinant human thymidine kinase 1 (TK1) with phosphorylation rates up to 89% relative to that of Thd. One compound out of this library, 3-[3-(7-NH(3)(+)-nido-m-carboran-1-yl)propan-1-yl]thymidine (19b), showed selective retention in TK1-expressing murine L929 wild-type tumors versus L929 TK1 (-) tumors in biodistribution studies. The biological evaluation of the zwitterionic NH(3)(+)-nido-m-carborane-substituted Thds indicated improved aqueous solubility and similar or even superior potential as BNCT agents compared with different classes of 3CTAs (Cancer Res. 2004, 64, 6280-6286 and 6287-6295). To complete previous structure-activity relationship (SAR) studies, 3-[(closo-o-carboranyl)methyl]thymidine (4) was also synthesized and evaluated.
    [Abstract] [Full Text] [Related] [New Search]