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

✍ Scribed by Daniel L. Klayman; Ai J. Lin; James M. Hoch; John P. Scovill; Chris Lambros; Arthur S. Dobek

• Book ID: 102916899
• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 539 KB
• Volume: 73
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600731226

✦ Synopsis

A series of 2-(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 thiosemicarbazides 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 (MIC, 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.