Boronated Nucleoside Bases

We will design and synthesize novel nucleic acid base derivatives containing cyanoborane group attached to a pyridine-type nitrogen atom of the purine or the pyrimidine cycle. The cyanoboronated bases may be designed to be more membrane soluble than the respective 2'- deoxyribonucleosides of known cytotoxic activities. In living organisms, these base derivatives may be converted to the 5'-nucleotides according to salvage pathways, even in cases when the respective 2'- deoxyribonucleosides are poor substrates for nucleoside kinases. Therefore, the cyanoboronated bases are expected to show better cytotoxic activities than the cyanoboronated 2'-deoxyribonucleosides and are feasible to use as antineoplastic agents. An additional importance is the potential for the compounds to be used in boron neutron capture therapy for the treatment of cancer. A rationale for the general synthetic approach to cyanoboronated nucleic acid bases is presented.