8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells

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Abstract
A variety of 8-substituted guanosine and 2''-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted -N(CH3)2, -NHCH3, -NH2, -OH and -SO2CH3, which caused 68, 42, 34, 33 and 30% of erythroleukemia cells to attain benzidine positivity, a functional measure of maturation, at concentrations of 5, 1, 0.4, 5 and 5 mM, respectively. The 8-OH derivative of the 2''-deoxyguanosine series produced comparable activity, causing 62% benzidine-positive cells at a level of 0.2 mM. 8-Substituted analogs of guanosine and 2''-deoxyguanosine evidently have the potential to terminate leukemia cell proliferation through conversion to end-stage differentiated cells.