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 antimycobacterial activity against Mycobacterium tuberculosis. Bioassay-guided fractionation of the crude extract led to the identification of (E)-phytol as the principal active component with a minimum inhibitory concentration (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)-and (2R,3R)-isomers of (E)-phytol epoxide and (3R,S,7R,11R)-phytanic acid displayed lower activities with MICs of 8, 16, and > 128 mu g/ml, respectively, 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 clinically useful drug with an MIC in the range 0.95-3.8 mu g/ml.