title: PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.
abstract: Naphthoquinones (NQs) occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness), Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found among Juglans spp. (Juglandaceae) with juglone derivatives as known constituents. In this study, 36 highly variable extracts were prepared from different plant parts of J. regia, J. cinerea and J. nigra. For all extracts, antiprotozoal activity was determined against the protozoans Trypanosoma cruzi, T. brucei rhodesiense and Leishmania donovani. In addition, an LC-MS fingerprint was recorded for each extract. With each extract's fingerprint and the data on in vitro growth inhibitory activity against T. brucei rhodesiense a Partial Least Squares (PLS) regression model was calculated in order to obtain an indication of compounds responsible for the differences in bioactivity between the 36 extracts. By means of PLS, hydrojuglone glucoside was predicted as an active compound against T. brucei and consequently isolated and tested in vitro. In fact, the pure compound showed activity against T. brucei at a significantly lower cytotoxicity towards mammalian cells than established antiprotozoal NQs such as lapachol.
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, PharmaCampus, Corrensstr. 48, Münster D-48149, Germany. therese.ellendorff@uni-muenster.de.
authors.forename: Therese
authors.initials: T
authors.lastname: Ellendorff
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstraße 57, Basel CH-4002, Switzerland. reto.brun@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. reto.brun@unibas.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstraße 57, Basel CH-4002, Switzerland. marcel.kaiser@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. marcel.kaiser@unibas.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, PharmaCampus, Corrensstr. 48, Münster D-48149, Germany. jandirk.sendker@uni-muenster.de.
authors.forename: Jandirk
authors.initials: J
authors.lastname: Sendker
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, PharmaCampus, Corrensstr. 48, Münster D-48149, Germany. thomschm@uni-muenster.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002853:Chromatography, Liquid; D020128:Inhibitory Concentration 50; D031324:Juglans / Q000737:chemistry*; D016018:Least-Squares Analysis; D007893:Leishmania donovani / Q000187:drug effects / Q000254:growth & development; D013058:Mass Spectrometry; D009285:Naphthoquinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D010936:Plant Extracts; C008252:lapachol; C005134:juglone
keywords: Juglandaceae; Juglans; LC-MS; Partial Least Squares; Trypanosoma brucei rhodesiense; hydrojuglone glucoside; naphthoquinones