Synthesis and characterization of nido-carborane-cobalamin conjugates.
Three vitamin B12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B12 binding capacity assay. When compared with 57Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.
Hogenkamp
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Department of Biochemistry, University of Minnesota, Minneapolis, USA. hogen001@tc.umn.edu
Collins
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DA
Live
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Benson
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LM
Naylor
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D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D003037:Cobalt Radioisotopes; D006801:Humans; D017247:Neutron Capture Therapy; D013329:Structure-Activity Relationship; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D001896:Boron Compounds; D003037:Cobalt Radioisotopes; D014805:Vitamin B 12