Anticancer activity of beta-L-dioxolane-cytidine, a novel nucleoside analogue with the unnatural L configuration.
Naturally occurring nucleosides and all anticancer nucleoside analogue drugs are in the beta-D configuration. L-(-)-dioxolane-cytidine [(-)-OddC] is the first L-nucleoside analogue ever shown to have anticancer activity. This compound was converted within cells to its mono-, di-, and triphosphate metabolites and was incorporated into DNA. As with cytosine arabinoside, conversion to the monophosphate was catalyzed by cellular deoxycytidine kinase, which was essential for cytotoxicity. However, unlike cytosine arabinoside, (-)-OddC was not susceptible to degradation by deoxycytidine deaminase. Because (-)-OddC inhibited the growth of hepatocellular and prostate tumors that are generally difficult to treat, it is a promising candidate for additional testing. Our results indicate that there is a great deal of variability in the chiral specificities of cellular enzymes and demonstrate how these differences can be exploited in the design of better anti-viral and anticancer drugs.[1]References
- Anticancer activity of beta-L-dioxolane-cytidine, a novel nucleoside analogue with the unnatural L configuration. Grove, K.L., Guo, X., Liu, S.H., Gao, Z., Chu, C.K., Cheng, Y.C. Cancer Res. (1995) [Pubmed]
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