STRUCTURE-ANTITUBERCULAR ACTIVITY RELATIONSHIP OF PHENOTHIAZINE-TYPE CALMODULIN ANTAGONISTS

Six neuroleptic (antipsychotic) phenothiazine derivatives which are ca lmodulin antagonists were tested for their activity against Mycobacter ium tuberculosis H(37)R(v) in order to understand their structure-anti tubercular activity relationship. Out of the six derivatives tested (t rifluoperazine, chlorpromazine, triflupromazine, thioridazine, acetopr omazine and fluphenazine), trifluoperazine appears to be a more potent antitubercular drug than others with a minimum inhibitory concentrati on (MIG) of 5 mu g/ml. Chlorpromazine, triflupromazine and thioridazin e are also active but less potent and have a higher MIC of 20 mu g/ml. Acetopromazine and fluphenazine could not completely inhibit the grow th even at a high concentration of 20 mu g/ml. These results indicate that a methylpiperazinylpropyl group attached to the nitrogen (positio n 10) atom and trifluoromethyl group at the second carbon confer antit ubercular activity to the phenothiazine molecule. It is suggested that trifluoperazine or one of its derivatives could be useful as one of t he drugs in the multi-drug regimen for the treatment of tuberculosis w ith psychotic problems or vice versa.