Trifluoperazine and CEF-allicin from garlic (Allium sativum) as potential new antitubercular drugs active against drug resistantMycobacterium tuberculosis

Abstract

Trifluoperazine (TFP) and a compound called CEF-allicin purified from garlic (Allium sativum) possess antitubercular activity against both drug susceptible and resistant clinical isolates ofMycobacterium tuberculosis. They are bactericidal in nature with multiple sites of primary action. This new use for known drug TFP was based on our observation that mycobacteria have calmodulin like protein which regulates their metabolism and a calmodulin antagonist has antitubercular activity. The minimum inhibitory concentration (MIC) of TFP againstM. tuberculosis was 4-5 μg/ml. It inhibited considerably by 6hrs, the synthesis of total lipids from(14)C-acetate and proteins and DNA as judged by the uptake of(14)C-glycine and(3)H-thymidine respectively by the bacilli. With 50 clinical isolates from our hospital at Delhi, the MIC was 4μg/ml, for 40% and 8μg/ml, for 50% of the isolates susceptible as well as resistant to one or more of the five drugs isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide. The MIC of CEF-allicin was 25μg/ml, for bothMycobacterium tuberculosis and isoniazid resistant clinical isolate TRC-C 1193. It inhibited in 6hrs or less the synthesis of total lipids completely and proteins and DNA ofM. tuberculosis from its labeled precursors almost completely.