2-Acetylpyridine Thiosemicarbazones. XI. 2-(Alpha-Hydroxyacetyl)Pyridine Thiosemicarbazones as Antimalarial and Antibacterial Agents

摘要

A series of 20(alpha-hydroxyacetyl)pyridine thiosemicarbazones was synthesized as potential antimalarial and antibacterial agents. Their synthesis was achieved by the condensation of N4-mono-or N4, N4-disubstituted thiosemicarbazid with 2-(alpha-hydroxyacetyl)pyridine. The latter was prepared by selective bromine oxidation of (2-pyridinyl)-1,2-ethanediol. The new compounds show potent inhibitory activity against penicillin-sensitive as well as penicillin-resistant Neisseria gonorrhoeae 8MIC, 0.5-0.004 micrograms/mL), against Neisseria meningitidis (MIC, 0.5-0.032 micrograms/mL), and Staphylococcus aureus (MIC, 0.5-2 micrograms/mL). Good In vitro antimalarial effects against Plasmodium falciparum (Smith strain; ID50, 6.7-38 ng/mL) were observed in most of these new agents, but only 3 of 12 compounds exhibit moderate in vivo activity against Plasmodium berghei. These new agents appear to be less toxic to the host and more water soluble than the corresponding 2-acetylpyridine thiosemicarbazones.