Synthesis and in vitro properties of trimethylamine- and phosphonate-substituted carboranylporphyrins for application in BNCT.
A series of carboranylporphyrins containing either amine or phosphonic acid functionalities and two to six closo-carborane clusters have been synthesized via a [2+2] condensation of a dimethylamino- or diethylphosphonate-substituted dipyrromethane with a dicarboranylmethyl-benzaldehyde. The X-ray structures of four key reaction intermediates (1, 2, 3, and 4a) and of two target porphyrins, the diphosphonate ester- and the diamino-tetracarboranylporphyrins 5b and 6a, are presented and discussed. In vitro studies using human carcinoma HEp2 and human glioblastoma T98G cells show that these porphyrins are non-toxic in the dark up to 100 microM concentrations, and that a tetracarboranylporphyrin bearing two quaternary ammonium groups is the most efficiently taken up by cells at short times (up to 8 h), followed by a dicarboranylporphyrin bearing three phosphonic acid substituents. All carboranylporphyrins delivered therapeutic amounts of boron to T98G cells and localized mainly within the cell lysosomes.
Easson
Michael W
MW
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803-1804, USA.
Fronczek
Frank R
FR
Jensen
Timothy J
TJ
Vicente
M Graça H
MG
D001896:Boron Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008744:Methylamines; D015394:Molecular Structure; D063065:Organophosphonates; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D001896:Boron Compounds; D008744:Methylamines; D063065:Organophosphonates; D011166:Porphyrins; C023336:trimethylamine