Synthesis and anticancer activity of asparagine analogs.
A series of 11 asparagines substituted on N4 was prepared and evaluated for their ability to inhibit the growth of L5178Y leukemia cell cultures. These cells require an exogenous source of L-asparagine and should be sensitive to an asparagine antimetabolite. The compounds were prepared by reaction of phthalylaspartic anhydride with a primary or secondary amine, followed by removal of the phthalyl group with hydrazine. One compound, N,N-dibenzylasparagine, showed significant activity. Additional study of asparagine derivatives bearing large, lipophilic groups at N4 is warranted.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D001216:Asparagine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001217:Aspartate-Ammonia Ligase / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D007940:Leukemia L5178 / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001216:Asparagine; D001217:Aspartate-Ammonia Ligase