Evaluation of antiparasitic activity of Mentha crispa essential oil, its major constituent rotundifolone and analogues against Trypanosoma brucei

Considering the pressing need for new drugs to treat sleeping sickness and nagana disease, Mentha crispa essential oil (MCOE), its principal constituent rotundifolone and four related p-menthane-type monoterpenes (two stereoisomers of limonene epoxide, perillyl alcohol and perillyl aldehyde) were investigated for their activity against bloodstream forms of Trypanosoma brucei. The general cytotoxicity of the compounds was determined with human myeloid HL-60 cells. The effect of the MCEO and the monoterpenes on the growth of parasite and human cells was evaluated in cell culture with the resazurin viability assay. Of all compounds tested, MCEO, rotundifolone and perillyl aldehyde showed the highest trypanocidal activities with 50% growth inhibition (GI50) and minimum inhibitory concentration (MIC) values of 0.3 μg/mL and 1 μg/mL, respectively. In contrast, HL-60 cells were considerably less sensitive to the compounds with MIC values of 100 μg/mL and GI50 values ranging between 3.4 to 13.8 μg/mL. As a consequence of this, GI50 and MIC ratios of cytotoxic to trypanocidal activity (selectivity index) of these three compounds were promising with values of 11-45 and 100, respectively. These results indicate that the p-menthane-type monoterpenes rotundifolone and perillyl aldehyde are interesting lead candidates for further rational anti-trypanosomal drug development.