title: Anti-Trypanosomatid Elemanolide Sesquiterpene Lactones from Vernonia lasiopus O. Hoffm.
abstract: Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples' lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid "protozoan" parasiteTrypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genusGlossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection. Therefore, the search for new efficacious, safe and affordable drugs is of high importance.Vernonia lasiopusO. Hoffm., an indigenous African plant of the Asteraceae family, has been extensively reported to be used ethno-medicinally as a treatment for malaria. Its crude extracts obtained with solvents of different polarity were screened in vitro for anti-protozoal activity and the dichloromethane extract was found to be particularly active againstTrypanosoma brucei rhodesiense(IC50= 0.17 µg/mL). Bioassay-guided chromatographic fractionation of the dichloromethane extract led to the isolation and identification of six elemanolide type sesquiterpene lactones: 8-desacylvernolide, vernolepin, vernomenin, vernodalol, vernodalin and 11,13-dihydrovernodalin. All these elemanolide sesquiterpene lactones showed in vitro anti-trypanosomal activity. They were also tested for cytotoxicity against mammalian cells (L6 cell line). Vernolepin, the main component in the extract, was also the most potent with an IC50value of 0.05 µg/mL againstT.b. rhodesiensetrypomastigotes. This compound showed a selectivity index of 14.5, which makes it an interesting candidate for in vivo tests and determination of its mechanism of action.
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany. m_kima01@uni-muenster.de.
authors.forename: Njogu M
authors.initials: NM
authors.lastname: Kimani
authors.affiliation: Department of Chemistry, Egerton University, P.O. Box 536, Egerton, Nairobi 20115, Kenya. josphat2001@yahoo.com.
authors.forename: Josphat C
authors.initials: JC
authors.lastname: Matasyoh
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, CH-4051 Basel, Switzerland. marcel.kaiser@unibas.ch.|University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland. marcel.kaiser@unibas.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, CH-4051 Basel, Switzerland. reto.brun@unibas.ch.|University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland. reto.brun@unibas.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany. thomschm@uni-muenster.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
mesh_terms: D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013057:Spectrum Analysis; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D035741:Vernonia / Q000737:chemistry*
chemical_list: D007783:Lactones; D010936:Plant Extracts; D014344:Trypanocidal Agents
keywords: Leishmania donovani; Plasmodium falciparum; Trypanosoma brucei rhodesiense; Trypanosoma cruzi; Vernonia lasiopus; antiprotozoal activity; elemanolide; sesquiterpene lactones