title: Evaluation of Antiparasitc Activity of Mentha crispa Essential Oil, Its Major Constituent Rotundifolone and Analogues against Trypanosoma brucei.
abstract: Considering the pressing need for new drugs to treat sleeping sickness and Nagana disease,Mentha crispaessential oil, its principal constituent rotundifolone, and four relatedp-menthane-type monoterpenes (two stereoisomers of limonene epoxide, perillyl alcohol, and perillyl aldehyde) were investigated for their activity against bloodstream forms ofTrypanosoma brucei. The general cytotoxicity of the compounds was determined with human myeloid HL-60 cells. The effect of theM. crispaessential oil and the monoterpenes on the growth of parasite and human cells was evaluated in cell cultures with the resazurin viability assay. Of all of the compounds tested,M. crispaessential oil, rotundifolone, and perillyl aldehyde showed the highest trypanocidal activities with 50 % growth inhibition (GI50) and minimum inhibitory concentration values of 0.3 µg/mL and 1 µg/mL, respectively. In contrast, HL-60 cells were considerably less sensitive to the compounds with minimum inhibitory concentration values of 100 µg/mL and GI50values ranging between 3.4 to 13.8 µg/mL. As a consequence of this, GI50and minimum inhibitory concentration 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 thep-menthane-type monoterpenes rotundifolone and perillyl aldehyde are interesting lead candidates for further rational antitrypanosomal drug development.
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Tamires Cardoso
authors.initials: TC
authors.lastname: Lima
authors.affiliation: Bob Champion Research and Education Building, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D027541:Mentha / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D039821:Monoterpenes; D009822:Oils, Volatile; D014344:Trypanocidal Agents; C032208:perillyl alcohol; C467828:rotundifolone