engleski

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 structure—function considerations, comparative conformational analysis was performed and X-ray structure analysis, molecular mechanics and molecular dynamics simulations were used in the search for the bioactive conformation(s). The cytotoxic effect of N, N-dimethyl-6-amino-6-deoxy-l-ascorbic acid on human tumour cell lines (Hep2, MiaPaCa2, HeLa) and on diploid human fibroblast (WI 38) was examined. The dimethylamino derivative of ascorbic acid expressed a stronger cytotoxic effect than ascorbic acid itself. This effect was cell-specific and dose dependent. The treatment of the cells with N, N-dimethyl-6-amino-6-deoxy-l-ascorbic acid probably resulted in apoptosis, evidenced by characteristic morphological changes and ladder DNA fragmentation. Apoptosis was not mediated by c-Myc or p53 proteins.

ascorbic acid derivatives ; synthesis ; modelling ; X-ray structure analysis ; cytotoxic effect

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