TRIFLUOPERAZINE INHIBITS THE INCORPORATION OF LABELED PRECURSORS INTOLIPIDS, PROTEINS AND DNA OF MYCOBACTERIUM-TUBERCULOSIS H37R(V)

We have recently demonstrated that the calmodulin antagonist trifluope razine has antitubercular activity in vitro against Mycobacterium tube rculosis H37R(v) susceptible and resistant to isoniazid. It is now sho wn that trifluoperazine at a concentration of 50 mug ml-1 when added t o the cells along with the labelled precursors inhibited the incorpora tion of [C-14]acetate into lipids (63%) and uptake of [C-14]glycine (7 4%) and [H-3]thymidine (52%) by whole cells of M. tuberculosis H37R, b y 6 h of exposure. After 48 h, the inhibition was 87%, 97% and 74%, re spectively. However, when the drug was added to cells taking up and me tabolizing the labelled precursors at a later point (3 h for [C-14]ace tate and [H-3]thymidine and 12 h for [C-14]glycine) it inhibited compl etely 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 t rifluoperazine has multiple sites of action and acts probably by affec ting the synthesis of lipids, proteins and DNA.