Relationship between the structure and cytotoxic activity of new unsaturated ketonucleosides tested on eight cell lines.

Article abstract of DOI:10.1016/0223-5234(87)90267-4

The synthesis and cytotoxic activity of 14 ketonucleosides on 8 normal, transformed and leukemic cell lines are described.Compounds 1, 2, 3, 4, 5, and 6 proved to be the most cytotoxic for transformed and leukemic cells; compound 7 presents an intermediate activity, whereas compounds 8, 9, 10, 11, 12, 13 and 14 exhibited little or no cytotoxicity. the presence of the or system in the sugar moiety of the molecule was required for cytotoxic activity.Introduction of bromine into the sugar moiety of compounds 1 made it highly toxic, whereas the introduction of an O-acetyl group into the sugar moiety of compound 5 seemed to moderate its cytotoxic activity.The degree of this activity was independent of the anomeric configuration, axial or equatorial position of the bases and the L or D configuration of the sugar.Ketonucleosides 1, 2, 3 and 5 inhibited DNA synthesis in leukemic REH₆ cells more markedly than RNA and protein syntheses. ketonucleosides / unsaturated ketonucleosides / cytotoxicity / macromolecular synthesis / structure-activity relationship