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

Bioorg Med Chem. 2005 Jul 1;13(13):4168-75. doi: 10.1016/j.bmc.2005.04.042.

Abstract

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 microM. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Boron Compounds / pharmacokinetics
  • Boron Compounds / pharmacology*
  • Boron Neutron Capture Therapy*
  • Cell Survival / drug effects*
  • Chlorocebus aethiops
  • Cricetinae
  • Fibroblasts / drug effects
  • Humans
  • Lung Neoplasms / drug therapy
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacokinetics
  • Thymidine / pharmacology
  • Tumor Cells, Cultured
  • Vero Cells

Substances

  • Boron Compounds
  • Thymidine