Carboranyl bisglycosides for the treatment of cancer by boron neutron capture therapy.
Boron neutron capture therapy is a special type of radiotherapy for the treatment of cancer by using boron compounds. Problems often arise from the low water solubility of these compounds, their unselective uptake into the cancer cells, and their toxicity. Here we describe the novel water-soluble ortho-carboranyl bisglycosides 7 and 10 containing either lactose or glucose and the mixed bisglycosides 1 and 28 containing glucose, mannose, and galactose. The carboranyl bisglycosides show almost no toxicity toward bronchial carcinoma cells of line A549 up to a concentration of 0.50 mM. As anticipated, these compounds exhibit nearly no uptake into C6 glioma cells; they can therefore be used for a selective delivery into malignant cells by using conjugates of glycohydrolases and monoclonal antibodies which bind to tumor-associated antigens, since by enzymatic hydrolysis the bisglycosides are transformed into lipophilic compounds.
Tietze
L F
LF
Institut für Organische Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany. ltietze@gwdg.de
Bothe
U
U
Griesbach
U
U
Nakaichi
M
M
Hasegawa
T
T
Nakamura
H
H
Yamamoto
Y
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D004187:Disaccharides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D006027:Glycosides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D015394:Molecular Structure; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001896:Boron Compounds; D004187:Disaccharides; D006027:Glycosides