ANTIMYCOBACTERIAL ACTIVITY OF (E)-PHYTOL AND DERIVATIVES - A PRELIMINARY STRUCTURE-ACTIVITY STUDY

The crude methanol extract of the Kenyan shrub Leucas volkensii Gurke (Labiatae) displayed in a radiorespirometric bioassay antimycobacteria l activity against Mycobacterium tuberculosis. Bioassay-guided fractio nation of the crude extract led to the identification of (E)-phytol as the principal active component with a minimum inhibitory concentratio n (MIG) of 2 mu g/ml, a value also observed for (3R,S,7R,11R)-phytanol , (Z)-phytol, and a commercially available 2:1 mixture of (E)-and (Z)- phytol, The derivatives (E)-phytol acetate, a mixture of the (2S,3S)-a nd (2R,3R)-isomers of (E)-phytol epoxide and (3R,S,7R,11R)-phytanic ac id displayed lower activities with MICs of 8, 16, and > 128 mu g/ml, r espectively, Geraniol and farnesol, displayed MICs of 64 and 8 mu g/ml , respectively. The activities of (E)-phytol, (Z)-phytol and (3R,S,7R, 11R)-phytanol were found to be in the same range as ethambutol, a clin ically useful drug with an MIC in the range 0.95-3.8 mu g/ml.