of the acetyl group had an overall negative effect on the antimalarial potency of this series of thiosemicarbazones.
Antibacterial Activity-In the assessment of the antibacterial activity of the 2-(a-hydroxyacetyl)pyridine thiosemicarbazones (Table Ill), the strong inhibitory effect of the 2-acetylpyridine thiosemicarbazones seen against N. gonorrhoeae and N. meningiiidis (3) was also observed here. Most of the 2-(a-hydroxyacetyl)pyridine compounds had MIC values of <O. 1 pg/mL against these bacterial species, and in a few instances the degree of inhibition Has slightly superior to that observed with the 2-acetylpyridine thiosemicarbazones.
Against S. aureus, several of the 2-(~-hydroxyacetyl)pyridine thiosemicarbazones, i.e., llf, h, and j, had MIC values of 0.5-I Fg/mL. Again, there were several instances in which inhibitory activity superior to the 2-acetylpyridine thiosemicarbaiones (i.e., in Ild, e, h, and k) was seen.
Conclusions
The biological data for the newly synthesized 2-(a-hydroxyacetyl)pyridine thiosemicarba7ones indicates that N4,N4-disubstitution provides optimal in uiuo and in uiiro antimalarial and antibacterial activities. The introduction of a hydroxy function into the a-position of 2-acetylpyridine thiosemicarbazones results in compounds with increased solubility, decreased host toxicity. and in some instances. improvement ofantimalarial and antibacterial activity in oirro. Howcvcr, this is offset by the concomitant decrease in in uiuo antimalarial effects. These results suggest that pharmacological parameters, such as tissue distribution and the rate of metabolism, play an essential role in determining the in ciuo antimalarial activity. as well as host toxicity, of this series of compounds. REFERENCES ( I ) D.