2-Acetylpyridine thiosemicarbazones XI: 2-(alpha-Hydroxyacetyl)pyridine thiosemicarbazones as antimalarial and antibacterial agents.
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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000962:Antimalarials / Q000138:chemical synthesis*; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D011725:Pyridines; D013882:Thiosemicarbazones