Effect on protein synthesis and cell survival of the benzaldehyde derivatives sodium benzylidene ascorbate (SBA) and the deuterated compound zilascorb(2H).
Three different benzaldehyde derivatives (viz. beta-cyclodextrin benzaldehyde inclusion compound (CDBA), 4, 6-O-benzylidene-D-glucose (BG) and sodium benzylidene-ascorbate (SBA) have been shown to exert anticancer effects in patients without causing side effects. The anticancer effects are, however, variable and in many cases weak. In a previous study we showed that benzaldehyde with a deuterated formyl group gave rise to a greater protein synthesis inhibition than nondeuterated benzaldehyde. Based on this deuterated benzaldehyde we have synthesized an ascorbic acid acetal; 5,6-benzylidene-d1-L-ascorbic acid (zilascorb(2H). In the present paper we compare the effect of this drug with respect to cell inactivation and inhibition of protein synthesis in human cells cultured in vitro with that of benzaldehyde, BG and SBA. It is shown that zilascorb (2H) is clearly the most effective of these drugs. The effect of zilascrob(2H) is reversible in the sense that protein synthesis regains its normal level shortly (i.e. within 1h) after removal of the drug. Even after protracted treatment inducing a cell kill of more than 99%, the few survivors appear to be without damage after removal of the drug.
Pettersen
E O
EO
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Larsen
R O
RO
Boerretzen
B
B
Dornish
J M
JM
Oftebro
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001547:Benzaldehydes / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003903:Deuterium; D006801:Humans; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001547:Benzaldehydes; D001597:Benzylidene Compounds; D003903:Deuterium; D001205:Ascorbic Acid; C070680:zilascorb; C032175:benzaldehyde