Abstract
In the course of our studies on antiprotozoal natural products and following our recent discovery that certain aminosteroids and aminocycloartanoid compounds from Holarrhena africana A. DC. (Apocynaceae) and Buxus sempervirens L. (Buxaceae), respectively, are strong and selective antitrypanosomal agents, we have extended these studies to another plant, related to the latter—namely, Pachysandra terminalis Sieb. and Zucc. (Buxaceae). This species is known to contain aminosteroids similar to those of Holarrhena and structurally related to the aminocycloartanoids of Buxus. The dicholoromethane extract obtained from aerial parts of P. terminalis and, in particular, its alkaloid fraction obtained by acid–base partitioning showed prominent activity against Trypanosoma brucei rhodesiense (Tbr). Activity-guided fractionation along with extended UHPLC-(+)ESI QTOF MS analyses coupled with partial least squares (PLS) regression modelling relating the analytical profiles of various fractions with their bioactivity against Tbr highlighted eighteen constituents likely responsible for the antitrypanosomal activity. Detailed analysis of their (+)ESI mass spectral fragmentation allowed identification of four known constituents of P. terminalis as well as structural characterization of ten further amino-/amidosteroids not previously reported from this plant.
Highlights
Human African Typanosomiasis (HAT or “sleeping sickness”) is a neglected tropical disease (NTD) caused by the kinetoplastid parasites Trypanosoma brucei gambiense andT. b. rhodesiense [1]
PS_AEF turned out to contain the active principle, since it was more than ten times more active than the crude extract against Trypanosoma brucei rhodesiense (Tbr), while the PS_NF was much less active
For preparative thin layer chromatography (TLC), the samples were applied as bands of 18 cm width and the plates developed over a distance of 18 cm
Summary
Human African Typanosomiasis (HAT or “sleeping sickness”) is a neglected tropical disease (NTD) caused by the kinetoplastid parasites Trypanosoma brucei gambiense andT. b. rhodesiense [1]. Human African Typanosomiasis (HAT or “sleeping sickness”) is a neglected tropical disease (NTD) caused by the kinetoplastid parasites Trypanosoma brucei gambiense and. Without treatment, this disease is inevitably fatal. As the few existing medications are toxic or difficult to administer, the search for new active chemical entities (CEs) against African trypanosomes remains an urgent goal. In spite of recent success with the introduction of the first orally active antitrypanosomal drug, Fexinidazole [2], it remains important to add new CEs with possibly new mechanisms of action to the drug development pipeline against T. brucei. We have discovered that certain aminosteroid alkaloids from an African Apocynacea, Holarrhena africana A. (a synonym of the more commonly used Holarrhena floribunda T.
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