Antimycobacterial activity of 2-acetylpyridine thiosemicarbazones in relation to their antileprosy activity.
Antimycobacterial assays were carried out on sixteen 2-acetylpyridine thiosemicarbazones using a number of culturable mycobacteria in vitro. The resulting MIC determinations were plotted against the lipophilicity (log P) values for the various test compounds. Plots of log MIC vs log P values conformed to a parabolic regression curve having a log Pmax of 4.0 for the slow-growing mycobacteria and 3.0 for the rapid grower, M. smegmatis. Ten thiosemicarbazone compounds covering a log P range of 1.0 to 4.5 were tested for their antileprosy activity in M. leprae-inoculated mouse foot pads. The resulting activity curve had a log Pmax of 2.0. The significance of these findings is discussed in terms of the role played by limiting diffusional factors within the tissue so far as the penetration of these thiosemicarbazones into the intracellular environment is concerned.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007917:Leprostatic Agents / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000494:pharmacology*
D007917:Leprostatic Agents; D013882:Thiosemicarbazones