title: Trifluoperazine inhibits the incorporation of labelled precursors into lipids, proteins and DNA of Mycobacterium tuberculosis H37Rv.
abstract: We have recently demonstrated that the calmodulin antagonist trifluoperazine has antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv susceptible and resistant to isoniazid. It is now shown that trifluoperazine at a concentration of 50 micrograms 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%) by whole cells of M. tuberculosis H37Rv 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.
authors.affiliation: Department of Biochemistry, University College of Medical Sciences and G.T.B. Hospital, Shahdara, Delhi, India.
authors.forename: P
authors.initials: P
authors.lastname: Ratnakar
authors.forename: P S
authors.initials: PS
authors.lastname: Murthy
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D050356:Lipid Metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014268:Trifluoperazine / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D014268:Trifluoperazine