Trifluoperazine inhibits the incorporation of labelled precursors into lipids, proteins and DNA of Mycobacterium tuberculosis H37Rv

We have recently demonstrated that the calmodulin antagonist trifluoperazine has antitubercular activity in vitro against Mycobacterium tuberculosis</it> H<inf>37</inf>R<inf>v</inf> susceptible and resistant to isoniazid. It is shown that trifluoperazine at a concentration of 50 μ g ml−1 when added to the cells along with the labelled precursors inhibited the incorporation of [14C]acetate into lipids (63%) and uptake of [14C]glycine (74%) and [3H]thymidine (52%) bu whole cells of M. tuberculosis</it> H<inf>37</inf>R<inf>v</inf> by 6 h of exposure. After 48 h, the inhibition was 87%, 97% and 74%, respectively. However, when the drug was added to cells taking up and metabolizing the labelled precursors at a later point (3 h for [14C]acetate and [3H]thymidine and 12 h for [14C]glycine) it inhibited completely the uptake of all the precursors, at least up to 24 h. The onset of inhibitory action was very rapid, i.e. 3 h. It is suggested that trifluoperazine has multiple sites of action and acts probably by affecting the synthesis of lipids, proteins and DNA.