Antitumor activity of alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil-5'-phosphate against murine lymphoma L5178Y resistant to 1-beta-D-ribofuranosyl-5-fluorouracil.
A 1-beta-D-ribofuranosyl-5-fluorouracil-resistant clone, designated L5178Y/FUR, was established in this experiment. This is one of the colonies derived from a subculture which acquired resistance to 1-beta-D-ribofuranosyl-5-fluorouracil by passaging the L5178Y cells through four sucessive episodes of culture in Fischers' medium containing 1-beta-D-ribofuranosyl-5-fluorouracil; each analog treatment was followed by recovery intervals. In this subline, IC99 values for 1-beta-D-ribofuranosyl-5-fluorouracil was 0.57 muM, which was 24 times as great as in the parent line (0.0024 muM), and this subline showed a cross resistance to 5-fluorouracil. New alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate (FUMP-alkylesters) were synthesized and their antitumor activity was examined against 1-beta-D-5-fluorouracil-sensitive and -resistant L5178Y sublines. Only hexadecylester of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate was effective, not only to 1-beta-D-ribofuranosyl-5-fluorouracil line but also to 1-beta-D-ribofuranolsyl-5-fluorouracil-resistant subline. Other compounds showed cross resistant in the 1-beta-D-ribofuranosyl-5-fluorouracil-resistant cells.
D000818:Animals; D000970:Antineoplastic Agents; D004351:Drug Resistance; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D014500:Uracil Nucleotides / Q000627:therapeutic use*; D014529:Uridine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014500:Uracil Nucleotides; C001943:5-fluorouridine; C016462:5-fluorouridine 5'-phosphate; D014529:Uridine