PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.

Molecules

Therese Ellendorff¹  Reto Brun²  Marcel Kaiser²  Jandirk Sendker¹  Thomas J. Schmidt¹ 

[1] Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, PharmaCampus, Corrensstr. 48, Münster D-48149, Germany; E-Mails:;Swiss Tropical and Public Health Institute (Swiss TPH), Socinstraße 57, Basel CH-4002, Switzerland; E-Mails:

关键词: Juglans;    Juglandaceae;    Trypanosoma brucei rhodesiense;    naphthoquinones;    hydrojuglone glucoside;    LC-MS;    Partial Least Squares;   

DOI  :  10.3390/molecules200610082

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.