title: Methotrexate analogues. 12. Synthesis and biological properties of some aza homologues.
abstract: Methotrexate analogues, in which an additional nitrogen atom is inserted between the phenyl ring and the carbonyl group of the side chain, were prepared by photochemical methods. The compounds were less inhibitory toward dihydrofolate reductase and thymidylate synthetase derived from Lactobacillus casei than was methotrexate. They were also less cytotoxic against human lymphoblastic leukemia cells (CCRF-CEM). In vivo against L-1210 leukemia in mice, the aza homologue of methotrexate showed significant antitumor activity (%ILS = 55%) compared to methotrexate (%ILS = 88%).
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D005493:Folic Acid Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007780:Lacticaseibacillus casei / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D007939:Leukemia L1210 / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008297:Male; D008722:Methods; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D013940:Thymidylate Synthase; D008727:Methotrexate