Potentiation of cytostatic effect of sulfur- or chlorine-containing purines and related ribonucleosides by amphotericin-B on cultured mouse leukemia cells.

Abstract

Synergistic effects of sulfur-containing purines and related ribonucleosides (6-thioinosine, 6-thioguanine, 6-thiocyanatopurine, 6-methylthioinosine, 6-thiocyanatoguanine, 6-thiocyanatoguanosine, 6-phenacylthioinosine, 6-nitrobenzlythioinosine, 6-(p-chlorobenzyl)thioinosine, 6-(p-nitrobenzyl)thioguanosine, 6-benzylthioinosine, 6-ethylthioinosine, 6-benzylthioguanine, 6-benzylthiopurine, 6-methylthiopurine, and 6-thiocyanatoinosine) and chlorine-containing purine and its ribonucleoside, (6-chloropuine and 6-chloropurine riboside), in combination with the polyene antibiotic, Amphotericin-B, on cell survival and synthesis of DNA were examined in mouse leukemia L5178Y cells. 6-Methylthioinosine, 6-thiocyanatopurine, 6-thiocyanatoinsoine, 6-methylthiopurine, and 6-thiocyanatoguanine (or -guanosine) among sulfur-containing compounds were strongly potentiated by Amphotericin-B, and 6-chloropurine riboside, which is electronically analogous to methylthioinosine, was also enhanced by the polyene. Thiocyanoto or methylthio group at position 6 of the purine ring seems to be important for the polyene-mediated potentiation. 6-Methylthioinosine alone had much greater effect on DNA synthesis of HeLa cells than on L5178Y cells, and Amphotericin-B failed to potentiate the action of 6-methylthioinosine in HeLa cells.