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.
Highlights
Protozoal infections are a major cause of suffering and death in tropical regions and especially in developing countries
Appeared an interesting group of plants to investigate for antiprotozoal activity
The reflection on Partial Least Squares (PLS) models with chemical fingerprints as independent and bioactivity data as dependent variables has proven suitable for the identification of bioactive compounds from complex extracts, thereby recommending itself as an alternative to bioassay-guided isolation
Summary
Protozoal infections are a major cause of suffering and death in tropical regions and especially in developing countries. NQs and other quinones may disturb the cellular redox status and thereby provoke the generation of reactive oxygen species (ROS) by redox cycling Because their redox metabolism significantly differs from that of other eukaryotic cells, protozoans of the family Trypanosomatidae are strongly impaired by ROS. ROS mainly arising from the photosynthetic apparatus of herbal materials under conditions of stress or senescence have been shown to significantly impact on secondary metabolites [8,9,10] Due to their susceptibility to chemical modifications by e.g., oxidative coupling we hypothesized that the oxidative environment provided in drying or senescing leaves of NQ-bearing plants should yield new NQ derivatives with possibly improved pharmacological properties.
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