SYNTHESIS AND BIOLOGICAL ACTIVITY OF CERTAIN 8-MERCAPTOPURINE AND 6-MERCAPTOPYRIMIDINE S-NUCLEOSIDES

S-Nucleosides were prepared by the reaction of acylglycosyl halides and the anions of certain 8-mercaptopurines and 6-mercaptopyrimidines. Among these, the adenosine analog 6-amino-8-(β-D-ribofuranosyl)thiopurine showed biological activity in the three test systems examined. It inhibited the in vitro growth of Escherichia coli by 50% at 5 × 10-6 M, and that of leukemia L1210 and Ehrlich ascites at 1 and 3 × 10-4 M, respectively. Comparative studies carried out in the E. coli systems with the S-nucleoside and with 8-mercaptoadenine and 8-mercaptoadenosine indicate that, in these cells, the S-glycoside linkage of the S-nucleoside remains intact. Further studies employing a partially purified preparation of adenosine deaminase revealed that the compound is not subject to deamination. An inhibition analysis showed that the inhibition of the growth of E. coli by the adenine S-riboside is partially preventable by the natural pyrimidines and to a greater extent by aspartate, but not by purines. © 1969, American Chemical Society. All rights reserved.