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N3-substituted thymidine bioconjugates for cancer therapy and imaging
Faculty
Science
Year:
2013
Type of Publication:
Article
Pages:
677-692
Authors:
Khalil, Ahmed, Tjarks, Werner, Ishita, Keisuke, Ali, Tehane
DOI:
10.4155/FMC.13.31
Journal:
FUTURE MEDICINAL CHEMISTRY FUTURE SCI LTD
Volume:
5
Research Area:
Pharmacology \& Pharmacy
ISSN
ISI:000319647000014
Keywords :
N3-substituted thymidine bioconjugates , cancer therapy , imaging
Abstract:
The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed.
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