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.

Antibacterial Properties of 2-Acetylpyridine-1-Oxide Thiosemicarbazones

“…In some instances the 1-oxides were virtually devoid of antibacterial properties when the parents were active. An impor tant corollary, however, is that the 1-ox ides are less toxic than the parent com pounds [11] which would make the former possibly more attractive as antibacterial agents.…”

“…Synthesis and physical properties of 2-acetylpyridine-1 -oxide thiosemicarbazones and thiosemicarbazides used in this study have been reported by Scovill et al [11]. The compounds were prepared by the Or ganic Synthesis Section, Division of Experimental Therapeutics, Walter Reed Army Institute of Re search.…”

New Copper(II) and Nickel(II) Complexes of 4‐Morpholinoaceto‐ phenone Thiosemicarbazone: Structural, Electrochemical and Antimicrobial Studies

“…All reactions were carried out under nitrogen in flame-dried glassware. 3 , the mixture was refluxed on a water bath for 4-6 h at 60 ℃. The precipitates formed were collected by filtration, washed with hot water and diethyl ether, and finally dried in a vacuum desiccator over silica gel (0.89 g, yield 74%).…”

“…1,2 Derivatives of thiosemicarbazones and their metal complexes were found to be active against influenza, protozoa, smallpox [3][4][5] and to have anticarcinogenic, antibacterial, and antifungal properties. [5][6][7][8] Recent studies revealed that a number of thiosemicarbazones possessed anticonvulsant activity.…”

Synthesis, characterization and Mössbauer studies of Fe(II) and Fe(III) complexes of 2-acetylpyridine thiosemicarbazone

“…The pharma co log i cal ac tiv ity of these com pounds has of ten been related to their che lat ing abil ity with metal ions 3 .…”