Synthesis and biological evaluation of some phosphate triester derivatives of the anti-cancer drug AraC
Open Access
- 25 September 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 17 (18) , 7195-7201
- https://doi.org/10.1093/nar/17.18.7195
Abstract
A number of novel phosphate triester derivatives of the anti-cancer nucleoside analogue araC have been prepared by a rapid 2-step procedure, not necessitating prior sugar protection. Spectroscopic and lipophilicity data have been collected on these compounds. An in vitro assay indicated inhibition of thymidine incorporation by mammalian epithelial cells, by each of these compounds, in the range 3–300μM. Moreover, the degree of inhibition showed a close correlation to chemical structure; in particular, there was a clear relationship between inhibition of thymidine incorporation and log(P). These results are consistent with cellular penetration by the intact phosphate triesters and intracellular action by an unspecified mechanism. Triethyl phosphate is inactive under the conditions of the testKeywords
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