2-Acetylpyridine thiosemicarbazones XI: 2-(α-hydroxyacetyl)pyridine thiosemicarbazones as antimalarial and antibacterial agents

Article abstract of DOI:10.1002/jps.2600731226

A series of 2-(α-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 thiosemicarbazides with 2-(α-hydroxyacetyl)pyridine. The latter was prepared by selective bromide oxidation of (2-pyridinyl)-1,2-ethanediol. The new compounds show potent inhibitory activity against penicillin-sensitive as well as penicillin-resistant Neisseria gonorrhoeae (MIC, 0.5-0.004 μg/mL), against Neisseria meningitidis (MIC, 0.5-0.032 μg/mL), and Staphylococcus aureus (MIC, 0.5-2 μg/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.