title: 2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents.
abstract: In view of the antimalarial activity in mice of 2-acetylpyridine thiosemicarbazones, a series of analogous 1-oxides was prepared for evaluation. Their synthesis was achieved by the reaction of 2-acetylpyridine 1-oxide with methyl hydrazinecarbodithioate to give methyl 3-[1-(2-pyridinyl 1-oxide)ethylidene]hydrazinecarbodithioate (II). Reaction of the latter intermediate with secondary amines afforded the desired 2-acetylpyridine 1-oxide thiosemicarbazones (III). Reduction of the azomethine linkage of II with NaBH4 gave methyl 3-[1-(2-pyridinyl 1-oxide)ethyl]-hydrazinecarbodithioate (IV) whose S-methyl group was then displaced by amines to give a 1-[1-(2-pyridinyl 1-oxide)ethyl]thiosemicarbazide, V. Antimalarial activity of III was evaluated against both Plasmodium berghei in the mouse and Plasmodium falciparum in an automated in vitro test system. In both cases, 2-acetylpyridine 1-oxide thiosemicarbazones were found to be less active than the corresponding de-1-oxide analogues. When compounds V were evaluated against Plasmodium berghei in the mouse, a diminution of activity was similarly seen in comparison to the analogues not bearing the 1-oxide moiety.
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D011725:Pyridines; D013882:Thiosemicarbazones; C033836:2-acetylpyridine thiosemicarbazone