Boron-containing polyamines as DNA targeting agents for neutron capture therapy of brain tumors: synthesis and biological evaluation

J Med Chem. 1997 Nov 21;40(24):3887-96. doi: 10.1021/jm960787x.

Abstract

Three series of new boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N1- and N5-(4-carboranylbutyl) SPD/SPM derivatives (SPD-1, SPD-5, SPM-1, SPM-5); N1,N10-diethyl-N5-(4-carboranylbutyl)spermidine (DESPD-5), N1,N14-diethyl-N5-(4-carboranylbutyl)spermine (DESPM-5); and N5,N10-bis(4-carboranylbutyl)spermine (SPM-5,10). In vitro studies using rat F98 glioma cells have shown that these polyamines retain the ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up by F98 glioma cells. However, their cytotoxicities, especially those with terminal N-substituted (SPD-1, SPM-1) boron compounds, are greater than those of SPD/SPM. Nevertheless, the groundwork has been created for a new class of boron-containing compounds that maybe useful for boron neutron capture therapy of tumors.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / pharmacokinetics
  • Boron Compounds / pharmacology*
  • Boron Neutron Capture Therapy / methods*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / radiotherapy*
  • DNA / drug effects*
  • DNA / metabolism
  • Female
  • Glioma / drug therapy
  • Glioma / radiotherapy*
  • Pregnancy
  • Rats
  • Rats, Inbred F344
  • Spermidine / analogs & derivatives*
  • Spermidine / chemical synthesis
  • Spermidine / pharmacokinetics
  • Spermine / analogs & derivatives*
  • Spermine / chemical synthesis
  • Spermine / pharmacokinetics
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Boron Compounds
  • Spermine
  • DNA
  • Spermidine