Correlations between structure and antimycobacterial activity in a series of 2-acetylpyridine thiosemicarbazones

The antimycobacterial activity of a new series of 2-acetylpyridine thiosemicarbazones was determined in vitro using Mycobacterium smegmatis ATCC 607. The resulting log minimal inhibitory concentration (μmol l^-1) values were plotted against the partition coefficient (log P) values for each compound, and fell on a parabolic distribution curve having a log P(opt) of 3.0. Compounds having partition coefficients outside the range 2.0 to 4.0 were inactive against M. smegmatis. When similar assays were carried out using M. tuberculosis, M. kansasii, M. marinum, M. simiae, M. avium and M. intracellulare, a similar series of parabolic activity curves were obtained having log P(opt) values aroung 4.0. The significance of this shift in the log P(opt) value obtained using the slow-growing pathogenic mycobacteria compared to that observed with the rapid-growing M. smegmatis is discussed in relation to the structures of the variable substituents of these new 2-acetylpyridine thiosemicarbazone compounds.