Effect on cell survival and protein synthesis of benzylidene-glucose (BG) and the deuterated analogue P-1013 in cultured cells.
4,6-Benzylidene-D-glucose (BG), is a known antitumour substance with low clinical toxicity. In order to increase the antitumour activity of BG a deuterated compound, 4,6-benzylidene-D-d1-glucose, denoted P-1013, was synthesised. P-1013 induced significantly greater cell inactivation than BG in mammalian cells of 10 different cell lines, implying that the deuteration of BG leads to increased cellular effects. Testing loss of colony forming ability following a 24 h exposure, the IC50 values, i.e. inhibitory doses that reduced the number of surviving treated cells by one half, were found to range from 3.2 to 10.8 mM BG and from 1.3 to 7.7 mM P-1013. In addition, P-1013 induced significantly greater inhibition of protein synthesis than BG in several of the tested cell lines. No cross-resistance to P-1013 or BG was seen in the MDR-positive colchicine-resistant KB-CHR-8-5 cell line compared with its parental cell line KB-3-1. Thus, the deuterated benzaldehyde derivative P-1013 is a reversible protein synthesis inhibitor inducing greater cellular effects than its undeuterated analogue BG in cultured mammalian cells.
Dunsaed
C B
CB
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo, Norway.
Dornish
J M
JM
Oftebro
R
R
Pettersen
E O
EO
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; C013844:benzylidene glucose; D005947:Glucose