Boron-containing polyamines as DNA targeting agents for neutron capture therapy of brain tumors: synthesis and biological evaluation.
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.
Cai
J
J
College of Pharmacy, Ohio State University, Columbus 43210, USA.
Soloway
A H
AH
Barth
R F
RF
Adams
D M
DM
Hariharan
J R
JR
Wyzlic
I M
IM
Radcliffe
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000532:radiotherapy*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013095:Spermidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013096:Spermine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001896:Boron Compounds; D013096:Spermine; D004247:DNA; D013095:Spermidine