Towards new boron carriers for boron neutron capture therapy:: metallacarboranes and their nucleoside conjugates

Thymidine conjugates containing metallacarborane, {8-[5-(N-3-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}(-) (5) and {8-[5-(O-4-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}(-) (6) ions and several simple [3-cobalt bis(1,2-dicarbollide)]- ion (1) derivatives have been studied as potential boron carriers for BNCT. Compound 6 and some nonnucleoside derivatives of 1 were not toxic above 100 mu M. The partition coefficient for both metallacarborane bearing thymidine conjugates 5 and 6 was more than 500 times higher than that of unmodified nucleoside. The cellular uptake studies showed accumulation of compounds 6 in V79 Chinese hamster cells but not of compound 5. The low toxicity of conjugate type of 6 together with its high partition coefficient suggest that judicially designed derivatives of metallacarboranes can be considered as potential boron carriers for BNCT. (c) 2005 Elsevier Ltd. All rights reserved.