Rifamycin Antibiotics: Inhibitors of Rauscher Murine Leukemia Virus Reverse Transcriptase and of Purified DNA Polymerases From Human Normal and Leukemic Lymphoblasts

The 201 rifamycin derivatives tested were classified into 8 groups according to common structural features and screened for inhibitory activity against human lymphocyte and murine leukemia virus DNA polymerases. On the basis of potency and selectivity, 10 compounds were selected for more detailed study with viral “reverse transcriptase” and normal and leukemic lymphocyte DNA pelymeroses I and II. Under all conditions tested, 3-(2,4-dinitrophenylhydrazonomethyl) rifamycin SV (144–126) and 3-piperazinoiminomethyl rifamycin SV (N-demethyl rifampicin) (143–416) had greater inhibitory effect against the viral polymerase than either normal cellular polymerase and preferentially inhibited leukemic polymerase II over normal polymerase II, though inhibition was not as great as with the viral enzyme. Several agents are potent inhibitors of both viral and cellular DNA polymerases, and some of these compounds consequently are of interest as antiviral and/or potential antileukemic agents.