SYNTHESIS, STRUCTURAL CHARACTERIZATION AND CYTOTOXIC EFFECT OF 6-AMINO-6-DEOXY-L-ASCORBIC ACID-DERIVATIVES

The synthesis, extended molecular modelling and cytotoxic effects of 6 -amino-6-deoxy-L-ascorbic acid derivatives are described. For structur e-function considerations, comparative conformational analysis was per formed and X-ray structure analysis, molecular mechanics and molecular dynamics simulations were used in the search for the bioactive confor mation(s). The cytotoxic effect of N,N-dimethyl-6-amino-6-deoxy-L-asco rbic acid on human tumour cell lines (Hep2, MiaPaCa2, HeLa) and on dip loid human fibroblast (WI 38) was examined. The dimethylamino derivati ve of ascorbic acid expressed a stronger cytotoxic effect than ascorbi c acid itself. This effect was cell-specific and dose dependent. The t reatment of the cells with N,N-dimethyl-6-amino-6-deoxy-L-ascorbic aci d probably resulted in apoptosis, evidenced by characteristic morpholo gical changes and ladder DNA fragmentation. Apoptosis was not mediated by c-Myc or p53 proteins.