Open AccessTrifluoperazine inhibits the incorporation of labelled precursors into lipids, proteins and DNA of Mycobacterium tuberculosis H 37 R v
Author(s) -
Ratnakar P.,
Suryanarayana Murthy P.
Publication year - 1993
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1993.tb06337.x
Subject(s) - trifluoperazine , mycobacterium tuberculosis , thymidine , isoniazid , in vitro , biochemistry , chemistry , glycine , dna , dna synthesis , mechanism of action , microbiology and biotechnology , calmodulin , biology , amino acid , tuberculosis , enzyme , medicine , pathology
We have recently demonstrated that the calmodulin antagonist trifluoperazine has antitubercular activity in vitro against Mycobacterium tuberculosis H 37 R v 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 [ 14 C]acetate into lipids (63%) and uptake of [ 14 C]glycine (74%) and [ 3H ]thymidine (52%) bu whole cells of M. tuberculosis H 37 R v 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 [ 14 C]acetate and [ 3 H]thymidine and 12 h for [ 14 C]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.