Potentiation of cytostatic effect of sulfur- or chlorine-containing purines and related ribonucleosides by amphotericin-B on cultured mouse leukemia cells.
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.
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002713:Chlorine; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006367:HeLa Cells; D007942:Leukemia, Experimental; D008778:Methylthioinosine / Q000494:pharmacology; D051379:Mice; D011687:Purines / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D013861:Thiocyanates / Q000494:pharmacology; D013866:Thioguanine / Q000494:pharmacology; D013868:Thioinosine / Q000494:pharmacology
D004273:DNA, Neoplasm; D011687:Purines; D012263:Ribonucleosides; D013861:Thiocyanates; D008778:Methylthioinosine; D013868:Thioinosine; D002713:Chlorine; D000666:Amphotericin B; D013866:Thioguanine