| Literature DB >> 16831554 |
Sureshbabu Narayanasamy1, B T S Thirumamagal, Jayaseharan Johnsamuel, Youngjoo Byun, Ashraf S Al-Madhoun, Elena Usova, Guirec Y Cosquer, Junhua Yan, Achintya K Bandyopadhyaya, Rohit Tiwari, Staffan Eriksson, Werner Tjarks.
Abstract
Five novel 3-carboranyl thymidine analogues (3CTAs) were designed and synthesized for boron neutron capture therapy (BNCT) of cancer. Phosphorylation of all five 3CTAs was catalyzed by recombinant human thymidine kinase (hTK1) using adenosine triphosphate (ATP) as the phosphate donor. The obtained phosphorylation rates ranged from 4% to 64.5% relative to that of thymidine. The compound with the most favorable hTK1 binding properties had a k(cat)/K(M) value of 57.4% relative to that of thymidine and an IC(50) of inhibition of thymidine phosphorylation by hTK1 of 92 microM. Among the five synthesized 3CTAs, this agent had also the overall most favorable physicochemical properties. Therefore, it may have the potential to replace N5-2OH, the current lead 3CTA, in preclinical studies. An in silico model for the binding of this compound to hTK1 was developed.Entities:
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Year: 2006 PMID： 16831554 DOI： 10.1016/j.bmc.2006.06.039
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641